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Morphogenesis

Morphogenesis is the biological process by which cells in a developing multicellular organism assemble into functional tissues and organs, generating the characteristic shapes and structures of the body through coordinated changes in cell behavior and tissue architecture.^[1] This process integrates genetic instructions with physical forces to transform a seemingly uniform mass of cells into complex forms, such as the folding of epithelial sheets or the elongation of embryonic axes.^[2] Central to morphogenesis are several key cellular mechanisms that drive tissue remodeling. Cell shape changes, such as apical constriction where the top of a cell narrows to bend tissues like in neural tube closure, enable folding and invagination.^[3] Cell movements, including migration and intercalation, allow tissues to rearrange and expand, as seen in the convergent extension during vertebrate body axis elongation.^[1] Proliferation and oriented cell division contribute to growth patterns, while programmed cell death and extrusion help sculpt boundaries and maintain epithelial integrity.^[1] These mechanisms are modulated by dynamic interactions between cells and the extracellular matrix (ECM), involving adhesion molecules like cadherins for cell-cell contacts and integrins for cell-ECM binding.^[3] Mechanical forces, such as tension and compression, arise from actomyosin contractility and ECM stiffness, influencing cell fate decisions and tissue rheology through transitions like fluid-to-solid jamming.^[3] In model organisms like Drosophila, epithelial elongation combines these elements to form segmented structures, highlighting how morphogenesis bridges molecular genetics and biophysics.^[1] Disruptions in these processes can lead to congenital defects.^[2]

Fundamentals

Definition and Scope

Morphogenesis is the biological process through which living organisms acquire their characteristic shapes and forms via the coordinated rearrangement, growth, and movement of cells and tissues during development.^[4] This process is distinct from cellular differentiation, which primarily involves the specialization of cells for specific functions, whereas morphogenesis emphasizes the spatial organization and architectural outcomes that give rise to multicellular structures such as tissues and organs.^[5] Early conceptualizations of morphogenesis, as proposed by figures like Caspar Friedrich Wolff, laid the groundwork for understanding development as an emergent property of progressive cellular organization.^[6] The scope of morphogenesis extends across eukaryotic organisms, encompassing key phases of development including embryonic patterning, organogenesis—the formation of functional organs—and regeneration, where tissues repair or reconstruct lost structures.^[7] In model organisms like the fruit fly Drosophila melanogaster, morphogenesis is exemplified by processes such as gastrulation and imaginal disc eversion, which sculpt the larval and adult body plan through precise tissue folding and extension.^[8] Similarly, the nematode Caenorhabditis elegans provides insights into invariant cell lineages and vulval induction, where cellular migrations and divisions generate reproducible organ forms despite environmental variations.^[9] Central principles guiding morphogenesis include positional information, differential growth, and invariance in patterning. Positional information refers to the mechanism by which cells interpret their spatial coordinates within a developing field to adopt context-specific behaviors, as originally conceptualized by Lewis Wolpert.^[10] Differential growth, highlighted in D'Arcy Wentworth Thompson's seminal analysis, arises from uneven rates of cellular proliferation and expansion, driving the transformation of simple forms into complex geometries, such as the curvature of vertebrate limbs or leaves. Invariance in patterning ensures that developmental outcomes remain robust and proportional across varying tissue sizes, achieved through mechanisms like morphogen gradient scaling that maintain consistent spatial cues.^[11]

Historical Development

The study of morphogenesis traces its roots to the 18th century, when German embryologist Kaspar Friedrich Wolff challenged the prevailing theory of preformation—the idea that organisms develop from miniature pre-existing forms—by proposing epigenesis, the gradual emergence of structures from unorganized material through observational studies of chick embryos.^[6] In his 1759 work Theoria Generationis, Wolff described how organs form progressively from a uniform blastoderm, laying the groundwork for understanding development as a dynamic process rather than a mere unfolding.^[12] By the 19th and early 20th centuries, researchers began incorporating mechanical principles to explain form generation. Swiss anatomist Wilhelm His advanced mechanical theories in the late 1800s, emphasizing differential tissue growth and tensions as drivers of embryonic shaping, using models like wax plates to simulate organ formation.^[13] This perspective influenced later biophysical views, with Scottish mathematician D'Arcy Wentworth Thompson's seminal 1917 book On Growth and Form introducing physical analogies—such as transformations via affine mappings—to compare biological shapes across species, highlighting how physical laws constrain organic morphology.^[14] The mid-20th century marked a shift toward chemical and informational models of pattern formation. In 1952, Alan Turing proposed the reaction-diffusion hypothesis in his paper "The Chemical Basis of Morphogenesis," suggesting that interacting diffusible substances could generate stable spatial patterns from uniform states, providing a mathematical framework for self-organizing biological forms.^[15] Building on this, developmental biologist Lewis Wolpert introduced the concept of positional information in 1969, positing that cells interpret their location in an embryo via gradients of signaling molecules to determine fate, as outlined in his theoretical paper on spatial cellular differentiation.^[10] From the late 20th century onward, morphogenesis research integrated genetics and advanced imaging, revealing molecular underpinnings of form. The discovery of Hox genes in the 1980s, conserved across animals and controlling body axis patterning, demonstrated how transcriptional regulators orchestrate regional identities during development.^[16] Concurrently, the adoption of confocal microscopy in the 1990s enabled three-dimensional visualization of dynamic embryonic processes, transforming observations from static sections to live, high-resolution reconstructions.^[17] Mechanical forces emerged as a recurring theme, linking historical biophysical ideas to genetic controls. In the 21st century, computational models from the 2000s onward simulated morphogenetic dynamics, bridging scales from genes to tissues. Recent milestones up to 2025 include enhanced live-cell imaging and optogenetics, allowing real-time manipulation and tracking of cellular behaviors; for instance, 2024 studies on Drosophila embryo folding used these tools to reveal trigger waves propagating tissue invaginations, and a May 2025 study demonstrated self-propagating waves driving morphogenesis of skull bones through mechanical feedback between cell fate and tissue stiffness in vivo.^[18]^[19]

Molecular and Genetic Mechanisms

Gene Regulatory Networks

Gene regulatory networks (GRNs) form the core of transcriptional control in morphogenesis, orchestrating the spatial and temporal expression of genes that drive developmental patterning. These networks are represented as directed graphs, with nodes corresponding to genes or transcription factors and directed edges indicating regulatory interactions, such as activation or repression between them. This structure allows GRNs to process inputs from maternal factors and integrate multiple signals to generate precise gene expression domains essential for tissue organization. Seminal work has emphasized that GRNs encode the causal logic of development, where cis-regulatory modules at target genes serve as computational units interpreting transcription factor inputs.^[20]^[21] A prominent example of GRN function in morphogenesis is the Hox gene clusters, which specify segmental identities along the body axis. In Drosophila melanogaster, the Antennapedia complex, part of the Hox cluster, regulates thoracic segment patterning by deploying homeodomain transcription factors that activate or repress downstream targets in a collinear manner. Mutations in this complex, as detailed in foundational genetic analyses, disrupt appendage and segment formation, highlighting the network's role in establishing anterior-posterior polarity. Hox GRNs exemplify hierarchical control, where upstream selectors like Antennapedia influence batteries of effector genes to sculpt morphological features.^[22] Feedback loops within GRNs enhance robustness and precision in patterning, often leading to bistable states that sharpen expression boundaries. In Drosophila embryogenesis, the maternal Bicoid gradient activates gap genes such as hunchback, which engage in mutual repression and autoactivation loops with other gap genes like Krüppel and knirps. These interactions generate bistable dynamics, where cells commit to distinct expression levels despite noisy inputs, ensuring reproducible segment positioning. Modeling studies confirm that such loops buffer against fluctuations in morphogen concentrations, promoting stable pattern formation.^[23] The segment polarity GRN further illustrates how feedback sustains periodic patterns within segments, with genes like wingless (encoding a Wnt ligand) and hedgehog maintaining mutual activation-repression circuits alongside engrailed. This network refines pair-rule gene outputs into 14 distinct parasegments, using short-range signaling to stabilize cell fates. Evolutionary analyses reveal deep conservation of this GRN across bilaterians, including arthropods and vertebrates, where orthologs of wingless and hedgehog retain roles in segmentation despite changes in deployment. Such conservation underscores the GRN's modularity, allowing morphological diversification while preserving core regulatory logic.^[24]^[25] Quantitative modeling of GRNs in morphogenesis frequently employs Hill functions to capture activation thresholds, describing the probability of gene expression as a sigmoidal function of transcription factor concentration:

f(X) = \frac{X^n}{K^n + X^n}

where X is the regulator concentration, K is the half-maximal activation threshold, and n (the Hill coefficient) controls response steepness, with higher n yielding sharper transitions critical for boundary formation. These functions enable simulations of pattern robustness, as seen in gap gene circuits where cooperative binding (n > 1) amplifies weak gradients into discrete domains.^[26]^[27]

Developmental Signaling Pathways

Developmental signaling pathways are essential intercellular communication mechanisms that orchestrate morphogenesis by transmitting positional and temporal cues to coordinate cell fate decisions, proliferation, and differentiation across tissues. These pathways typically involve the secretion of ligands that bind to specific receptors on target cells, triggering intracellular cascades that modulate gene expression and cellular behaviors. In morphogenesis, such signaling ensures the precise spatial organization of embryonic structures, from axis establishment to organ formation, by integrating extrinsic signals with intrinsic cellular responses.^[28] Among the major pathways, Wnt/β-catenin signaling plays a pivotal role in embryonic axis formation, particularly along the anterior-posterior and dorsal-ventral axes in vertebrates. In this canonical pathway, Wnt ligands bind to Frizzled receptors and LRP5/6 co-receptors on the cell surface, leading to the inhibition of the β-catenin destruction complex (comprising Axin, APC, GSK3β, and CK1). This stabilization allows β-catenin to accumulate in the cytoplasm, translocate to the nucleus, and activate transcription factors like TCF/LEF to drive target gene expression, such as those involved in cell fate specification during gastrulation. For instance, in Xenopus embryos, maternal Wnt/β-catenin signaling establishes the Nieuwkoop center, initiating dorsal axis formation by inducing organizer genes.^[29]^[30]^[31] Notch signaling, in contrast, mediates short-range, cell-cell interactions critical for lateral inhibition, where it refines patterns by promoting alternate cell fates in adjacent cells during neurogenesis and somitogenesis. Delta-like or Jagged ligands on one cell activate Notch receptors (Notch1-4 in mammals) on neighboring cells, triggering sequential proteolytic cleavages by ADAM metalloproteases and γ-secretase to release the Notch intracellular domain (NICD). NICD then translocates to the nucleus, forming a complex with RBPJ and co-activators like Mastermind to repress proneural genes (e.g., via Hes/Hey transcription factors) in signal-receiving cells, thereby amplifying differences in ligand expression and generating salt-and-pepper patterns of differentiation. This mechanism is exemplified in Drosophila neuroblasts and vertebrate neural progenitors, where stochastic fluctuations in ligand levels are amplified into stable fate boundaries.^[32]^[33]^[34] BMP and TGF-β signaling pathways contribute to dorsoventral patterning by establishing opposing gradients that specify ventral and dorsal fates, respectively, in the embryonic ectoderm and mesoderm. BMP ligands (e.g., BMP4, BMP7) bind to type I (ALK1-7) and type II (BMPRII) serine/threonine kinase receptors, recruiting and phosphorylating receptor-regulated Smads (R-Smads 1/5/8), which complex with Smad4 and translocate to the nucleus to activate ventralizing genes like ventx in Xenopus. Antagonists such as Chordin and Noggin, secreted from the dorsal organizer, create a BMP gradient that decreases ventrally, interpreting threshold concentrations to pattern tissues; high BMP promotes epidermal fates, while low levels induce neural plate formation. TGF-β ligands (e.g., Nodal, Activin) similarly signal through ALK4/5/7 and ActRII receptors to phosphorylate Smads 2/3, driving mesendoderm induction in a complementary manner.^[35]^[36]^[37] Morphogen gradients, where signaling molecules diffuse to form concentration profiles interpreted by cells in a concentration- and duration-dependent manner, are central to patterning, as illustrated by the French flag model proposed by Lewis Wolpert. In the vertebrate neural tube, Sonic Hedgehog (Shh), secreted from the notochord and floor plate, forms a ventral-to-dorsal gradient that patterns neuronal subtypes via Patched/Smoothened receptors, activating Gli transcription factors; high Shh induces floor plate (Gli activators), intermediate levels specify motor neurons (Gli balanced), and low levels ventral interneurons (Gli repressors). Gradient establishment involves restricted Shh sources, diffusion modulated by proteoglycans like heparan sulfate, and degradation by Hip1, ensuring precise boundary formation within the first ~50 μm from the floor plate in chick embryos. Cells interpret these gradients through temporal integration, where prolonged exposure to threshold levels commits fates, upstream of gene regulatory networks and downstream effectors like cytoskeletal regulators.^[38]^[39]^[40] Crosstalk between pathways enhances morphogenetic precision, as seen in Wnt-Notch interactions during somitogenesis, where oscillating Wnt signaling in the presomitic mesoderm (PSM) drives cyclic expression of Notch targets like Hes7, synchronizing segmentation clocks across cells. In mouse PSM, Wnt3a stabilizes β-catenin to induce Fgf and Notch components, while Notch activation feeds back to modulate Wnt via Lef1, creating phase-shifted oscillations (~2-3 hours per cycle) that determine somite boundaries through Mesp2 stripes. This integration ensures robust wavefront-propagation models, where FGF gradients set the pace.^[41]^[42]^[43] A species-specific example is FGF signaling in vertebrate limb bud outgrowth, where Fgf8 and Fgf10 from the apical ectodermal ridge (AER) and lateral plate mesoderm, respectively, form a feedback loop to drive proximodistal elongation. FGFs bind FGFR1-4 tyrosine kinase receptors, activating MAPK/ERK cascades via FRS2 and Ras to promote proliferation and inhibit differentiation in the progress zone, with graded signaling (high distally) specifying proximal structures first. In chick and mouse, this loop integrates with Shh from the zone of polarizing activity for anteroposterior patterning, ensuring coordinated bud extension over days of development.^[44]^[45]^[46]

Cellular Processes

Cell Adhesion and Junctions

Cell adhesion molecules and junctions are essential for maintaining tissue integrity and enabling dynamic shape changes during morphogenesis by mediating specific cell-cell interactions. These structures allow cells to adhere stably while responding to mechanical and biochemical cues, facilitating processes like tissue folding and invagination. In epithelial tissues, junctions form a belt-like network that anchors the cytoskeleton and regulates paracellular permeability, ensuring coordinated cellular behaviors critical for embryonic development.^[47] Adherens junctions, primarily composed of cadherins such as E-cadherin linked to the actin cytoskeleton via catenins, provide dynamic adhesion that supports tissue cohesion and morphogenesis. Tight junctions, involving proteins like occludins and claudins, seal the intercellular space to establish epithelial barriers and polarity, which is vital for compartmentalization during organ formation. Desmosomes, featuring desmogleins and desmocollins connected to intermediate filaments, offer robust mechanical strength to withstand tensile forces in tissues undergoing deformation. These junction types collectively ensure structural stability while permitting remodeling essential for developmental progression.^[48]^[49] A key role of cell adhesion occurs during epithelial-mesenchymal transitions (EMT), where downregulation of E-cadherin reduces cell-cell adhesion, enabling cells to detach and migrate while adopting a mesenchymal phenotype. This process is crucial for events like neural tube closure and mesoderm formation, allowing cells to contribute to multiple tissue layers. In neural crest development, cadherin switching from E-cadherin to N-cadherin facilitates delamination, as N-cadherin expression promotes motility and invasion into surrounding tissues without complete loss of adhesion. Such switches maintain partial connectivity, preventing excessive dispersion during morphogenesis.^[50] Adhesion dynamics are further modulated by mechanical forces, where catch bonds in cadherin-mediated junctions strengthen under tension, enhancing stability in actively remodeling tissues. This force-dependent behavior allows junctions to adapt to shear stresses during tissue elongation and convergence. For instance, in Xenopus gastrulation, cadherin-based adhesions at the blastopore lip coordinate involution movements, ensuring precise mesendoderm migration while preserving epithelial integrity. Wnt signaling briefly regulates these adhesions by influencing cadherin trafficking and junction assembly.^[51]^[52]^[53]

Extracellular Matrix Interactions

The extracellular matrix (ECM) serves as a dynamic scaffold in morphogenesis, providing structural support and biochemical cues that guide cell behavior and tissue remodeling during development. Composed primarily of fibrous proteins, glycoproteins, and proteoglycans, the ECM influences processes such as cell migration, differentiation, and patterning by interacting with cell surface receptors and modulating the local microenvironment.^[54] Key ECM components include collagens, which form the structural backbone of interstitial matrices and basement membranes, offering tensile strength to tissues undergoing shape changes. Laminins, prominent in basement membranes, promote cell adhesion and signaling essential for epithelial organization in organogenesis. Proteoglycans, such as those containing heparan or chondroitin sulfate chains, regulate growth factor binding and diffusion, while fibronectin, a multifunctional glycoprotein, assembles into fibrils that stabilize basement membranes and facilitate cell traction during morphogenetic movements.^[54]^[55] Integrin-mediated adhesion links the ECM to the intracellular cytoskeleton via focal adhesions, enabling cells to sense and respond to matrix stiffness and composition during tissue morphogenesis. These transmembrane receptors, such as α5β1 integrin binding to fibronectin, cluster at focal adhesions to transmit mechanical signals that drive cytoskeletal reorganization and directed cell motility in processes like gastrulation and neural tube closure.^[56] ECM remodeling is orchestrated by matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases that degrade and restructure matrix components to accommodate tissue invasion and reshaping. For instance, MMP-2 and MMP-9 cleave collagens and laminins, facilitating epithelial-mesenchymal transitions and branching in lung and kidney development. Biochemical gradients within the ECM provide spatial cues for cell guidance, with hyaluronic acid (HA) forming concentration gradients that influence neural development by modulating cell proliferation and migration. In the embryonic brain, HA gradients, synthesized by hyaluronan synthases, create hydrated matrices that support axonal pathfinding and cortical layering, while its degradation by hyaluronidases refines these patterns.^[57] In somite segmentation, the ECM contributes to boundary formation through fibronectin assembly, which guides posterior-to-anterior cell rearrangements and stabilizes nascent somite interfaces. Integrin α5-mediated interactions with fibronectin ensure proper somite rotation and epithelialization, preventing fusion between adjacent segments during vertebrate axial patterning.^[58]^[59]

Cytoskeletal Dynamics and Contractility

Cytoskeletal dynamics in morphogenesis are primarily driven by actin filaments and non-muscle myosin II motors, which form actomyosin networks capable of generating contractile forces essential for cell shape changes and tissue deformation.^[60] Actin polymerization provides the structural scaffold, while myosin II crosslinks and slides actin filaments to produce tension, regulated by pathways such as RhoA and its effector ROCK (Rho-associated coiled-coil containing protein kinase). RhoA activation recruits ROCK, which phosphorylates the regulatory light chain of myosin II to enhance contractility and inhibits myosin phosphatase to sustain force generation.^[60] These components enable dynamic remodeling, where actomyosin networks assemble and disassemble to drive localized deformations during development.^[61] Contractile mechanisms often involve pulsatile actomyosin activity, particularly in apical constriction, where medial apical networks contract intermittently to reduce cell apical surface area. In the Drosophila ventral furrow invagination, this process is exemplified by asynchronous pulses of myosin II coalescence in the medial apical cortex, followed by ratcheting pauses that stabilize the constricted state through actomyosin reinforcement at junctions.^[61] This pulsatile mode allows progressive constriction without full relaxation, integrating with adherens junctions to transmit forces across cells, ultimately folding the mesodermal primordium.^[61] Microtubules contribute to morphogenesis by orienting the mitotic spindle during asymmetric cell divisions, ensuring proper cell fate segregation and tissue organization. Astral microtubules interact with cortical dynein and the NuMA/LGN complex to generate pulling forces that align the spindle along polarity axes, as seen in Drosophila neuroblasts where apical-basal orientation via Pins/Mud proteins directs neuroblast renewal and ganglion mother cell specification.^[62] Actomyosin flows represent coordinated cytoskeletal movements that generate directional stresses for tissue remodeling. These flows arise from myosin-driven sliding of actin filaments, producing tensile stresses on the order of nanonewtons that deform cells and junctions. In convergent extension during zebrafish gastrulation, mediolateral actomyosin contractility, regulated by planar cell polarity signaling and RhoA/ROCK, drives polarized intercalations, enabling axial narrowing and elongation of the mesoderm. This process highlights how intracellular force generators scale tissue-level changes, with myosin II pulses facilitating vertical and horizontal intercalations.

Cell Migration and Morphogenetic Movements

Cell migration is a fundamental process in morphogenesis, enabling the coordinated rearrangement of cells to shape tissues and organs during embryonic development. Morphogenetic movements involve the directed translocation of cells or groups of cells, driven by intrinsic cellular programs and extrinsic cues, to generate tissue architecture. These movements are essential for processes such as tissue folding, elongation, and branching, ensuring proper organ formation.^[63] Collective cell migration occurs when groups of cells move cohesively while maintaining cell-cell contacts, allowing tissues to reshape without disrupting integrity. A prominent example is the migration of the lateral line primordium in zebrafish, where a stream of epithelial cells deposits sensory organs as it migrates posteriorly, guided by chemokine signaling to coordinate leader-follower dynamics.^[64] In contrast, individual cell migration involves cells detaching and moving independently through the extracellular matrix, exemplified by neural crest cells in vertebrates. These multipotent cells delaminate from the neural tube, undergo epithelial-to-mesenchymal transition, and migrate long distances to contribute to diverse derivatives like peripheral neurons and craniofacial structures, directed by repulsive and attractive cues from the environment.^[65] Key morphogenetic movements include invagination, where epithelial sheets fold inward to form structures like the neural tube during neurulation; evagination, the outward bulging of tissues such as the optic vesicle; and convergent extension via cell intercalation, which elongates tissues during gastrulation by cells rearranging mediolaterally. In gastrulation, involuting mesendodermal cells intercalate to narrow and extend the embryo, while in neurulation, apical constriction facilitates neural plate bending and invagination. These movements rely on adhesion for cohesion and contractile machinery for propulsion, but their coordination produces multicellular outcomes.^[66]^[67] Guidance of these migrations often involves chemotaxis, where cells respond to soluble gradients of signaling molecules like VEGF, and haptotaxis, where immobilized ligands in the extracellular matrix create substrate-bound gradients that direct cell orientation and speed. For instance, in angiogenic sprouting during vascular development, endothelial tip cells lead sprout invasion via filopodia sensing VEGF gradients, promoting directional migration while stalk cells proliferate to elongate the vessel.^[68]^[69] Quantitative analysis of morphogenetic flows reveals metrics such as migration velocity, typically ranging from 0.1 to 1 μm/min in collective epithelial sheets, and directionality, measured by persistence ratios indicating sustained movement over random diffusion. In zebrafish gastrulation, mesendoderm progenitors exhibit high directionality (persistence >0.8) aligned with tissue flows, ensuring efficient tissue spreading. These parameters highlight how local cell behaviors scale to global tissue remodeling.^[70]^[71]

Biophysical Aspects

Mechanical Forces in Tissues

Mechanical forces play a pivotal role in shaping tissues during morphogenesis, where cells generate and respond to physical stresses that drive tissue deformation and organization. These forces arise from cellular contractility and extracellular interactions, enabling coordinated movements at the tissue scale. In vertebrate embryos, for instance, forces contribute to processes like gastrulation and neural tube formation by altering cell shapes and positions.^[72] Tissues experience various types of mechanical forces, including tensile forces that stretch and elongate structures, compressive forces leading to buckling instabilities, and shear forces that promote sliding between cell layers. Tensile forces, often generated by actomyosin contractility, facilitate tissue extension, as seen in the elongation of the Drosophila embryo during germband extension. Compressive forces can induce buckling in epithelial sheets, contributing to invagination events, while shear stresses enable relative motion between tissues, such as in convergent extension movements. These force types integrate to sculpt complex architectures, with their magnitudes typically ranging from nanonewtons at the cellular level to micronewtons across tissues.^[73] Mechanotransduction pathways allow cells to sense and respond to these forces, translating mechanical cues into biochemical signals that regulate gene expression and cell fate. A key mechanism involves the YAP/TAZ transcriptional regulators, which are activated by substrate stiffness and cytoskeletal tension, promoting nuclear localization and driving proliferation or differentiation in response to tissue mechanics. In skeletal morphogenesis, YAP/TAZ signaling integrates Hippo pathway inputs to control chondrocyte proliferation and matrix production under mechanical load. Dysregulation of YAP/TAZ can lead to aberrant tissue patterning, highlighting their role in force-mediated development.^[74]^[75] Tissue rheology, encompassing the viscoelastic properties of embryonic tissues, governs how forces propagate and dissipate during folding and remodeling. Viscoelasticity allows tissues to exhibit both elastic recovery and viscous flow, enabling reversible deformations under stress while permitting irreversible shape changes over time. Recent studies on the Drosophila embryo reveal that during cephalic furrow formation, a mechanical wave propagates along a genetic guide, with viscoelastic relaxation facilitating coordinated folding and preventing mechanical instabilities. These properties vary spatiotemporally, with blastoderm cells rapidly adjusting viscosity to drive morphogenetic transitions, as quantified by atomic force microscopy showing moduli shifts from 10-100 Pa within minutes.^[76]^[77] To quantify these forces, techniques like traction force microscopy (TFM) have become essential, measuring substrate deformations to infer cellular stresses in living tissues. TFM uses deformable gels embedded with fluorescent beads to map traction vectors, revealing stress patterns during epithelial morphogenesis with resolutions down to 1-10 nN/μm². Advanced variants, including monolayer stress microscopy, extend this to intercellular forces, providing insights into how tensions coordinate tissue-scale behaviors without perturbing development.^[78] Across kingdoms, mechanical forces manifest similarly; in plants, osmotic pressure drives cell expansion by generating turgor that stretches the cell wall, influencing organ morphogenesis like leaf and root growth. Turgor gradients, reaching 0.5-1 MPa, create directional forces that orient cellulose deposition, ensuring anisotropic expansion essential for tissue patterning. Contractility from cytoskeletal elements serves as a primary force source, while the extracellular matrix transmits these stresses across tissues.^[79]^[80]

Pattern Formation Mechanisms

Pattern formation in morphogenesis arises from self-organizing chemical and physical processes that generate spatial order in developing tissues, often through instabilities that break initial uniformity.^[15] These mechanisms, independent of external templates, rely on local interactions propagating across scales to produce periodic or hierarchical structures like stripes, spots, or folds.^[81] A foundational mechanism is the reaction-diffusion system, proposed by Alan Turing, where interacting chemical substances—termed morphogens—diffuse and react to form stable patterns via diffusion-driven instability.^[15] In this activator-inhibitor framework, an activator promotes its own production while an inhibitor suppresses it, with the inhibitor diffusing faster than the activator, leading to emergent spatial heterogeneity.^[81] The dynamics are described by the Turing equations:

\frac{\partial u}{\partial t} = D_u \nabla^2 u + f(u,v)

\frac{\partial v}{\partial t} = D_v \nabla^2 v + g(u,v)

where u and v represent activator and inhibitor concentrations, D_u and D_v are their diffusion coefficients (D_v > D_u), and f and g are nonlinear reaction terms.^[15] Such systems can produce stripes or spots, as seen in zebrafish pigmentation where short-range activation and long-range inhibition generate periodic bands.^[82] Morphogen gradients further interpret these patterns through concentration-dependent thresholds that trigger differential gene expression, resulting in distinct cellular fates.^[83] For instance, in vertebrate somitogenesis, Delta-Notch signaling oscillates to create stripes of somites; cyclic activation of Delta ligands and Notch receptors in neighboring cells produces synchronized waves of gene expression (e.g., Hes7), with high Notch activity defining somite boundaries via inhibitory feedback.^[84] These oscillations, period-matched to somite formation timing (about 2 hours in mice), ensure periodic patterning along the anterior-posterior axis.^[83] Physical instabilities, such as buckling and folding under compressive forces, also drive pattern formation in epithelial sheets and tubes.^[85] When growing tissues confined by surrounding structures experience differential expansion, compressive stress induces mechanical buckling, forming wrinkles or folds that establish tissue architecture.^[86] In the vertebrate gut, for example, epithelial proliferation outpaces mesenchymal growth, leading to buckling instabilities that compartmentalize the intestine into regions with distinct morphologies.^[86] Experimental studies validate these mechanisms through precise lineage tracing, as in the nematode Caenorhabditis elegans, where 2025 high-resolution cellular maps reveal invariant embryonic patterning across individuals.^[87] Covering over 95% of embryonic cells, these maps demonstrate reproducible spatial organization from early cleavages, underscoring the robustness of self-organizing rules in achieving pattern invariance despite stochastic noise.^[88] In plants, auxin transport generates pattern maxima that dictate organ positioning in phyllotaxis, the spiral arrangement of leaves or flowers.^[89] Polar auxin flow via PIN-FORMED carriers creates localized peaks at future primordia sites on the shoot apical meristem, inhibiting new maxima nearby through depletion and feedback, thus establishing divergent angles (e.g., 137.5° Fibonacci spirals) for optimal packing.^[90]

Specific Morphogenetic Processes

Branching Morphogenesis

Branching morphogenesis is an iterative developmental process that generates highly branched tubular structures in organs such as the lungs and kidneys, enabling efficient surface area expansion for gas exchange and filtration.^[91] In the lungs, it begins with the outgrowth of primary bronchial buds from the foregut endoderm around embryonic day 9.5 in mice, followed by repeated branching to form the tracheobronchial tree and eventual alveolarization. Similarly, in the kidneys, the ureteric bud emerges from the Wolffian duct at embryonic day 11 and undergoes successive bifurcations to form the collecting duct system, interacting with metanephric mesenchyme to induce nephron formation.^[92] The process unfolds in distinct stages: initiation, where epithelial buds form in response to mesenchymal signals; elongation, involving directed growth of bud tips through cell proliferation and migration; and bifurcation, marked by the splitting of tips into new branches.^[91] Central to bifurcation is the differentiation of tip cells, which remain proliferative and migratory, from stalk cells that form the structural duct and undergo differentiation.^[91] Tip cells exhibit high expression of receptors for growth factors, driving selective outgrowth, while stalk cells contribute to lumen formation and stabilization. In the lung, this differentiation ensures asymmetric branching patterns, with tips exploring space stochastically before splitting at a constant probability.^[91] Brief references to cell migration at tips and extracellular matrix remodeling during elongation support this spatial organization without dominating the process. Key drivers include fibroblast growth factor 10 (FGF10), secreted by mesenchymal cells, which promotes epithelial bud outgrowth and branching in both lung and kidney by activating FGFR2b receptors on tip epithelium, leading to proliferation and invasion.^[92] In vascular branching, vascular endothelial growth factor (VEGF) guides endothelial tip cell selection and sprouting, with spatially restricted VEGF-A isoforms directing branch patterning and network formation essential for angiogenesis.^[93] Mechanical feedback integrates with these signals to regulate branching geometry. In lung ducts, lumen pressure buildup induces epithelial buckling and cleft formation, promoting bifurcation, while curvature-sensing via ERK signaling in tip cells modulates growth direction to maintain optimal spacing.^[94] Quantitative analyses reveal stereotypic branching angles of approximately 100–115 degrees in early lung bifurcations, transitioning to more variable angles in later generations, contributing to space-filling fractal-like structures that maximize surface area efficiency. In kidneys, dichotomous branching yields fractal-like structures reflecting compact organ filling compared to the lung's more extended structure. Aberrant branching underlies pathological conditions like polycystic kidney disease (PKD), where mutations in PKD1 or PKD2 disrupt convergent extension and oriented cell divisions during ureteric bud morphogenesis, leading to excessive lateral branching and cyst formation instead of proper elongation.^[95] In PKD models, loss of polycystin signaling impairs tip-stalk patterning, resulting in dilated ducts and reduced nephron induction.^[95]

Organ and Tissue Formation

Organogenesis integrates cellular and molecular mechanisms to form complex three-dimensional organ structures during embryogenesis, progressing through distinct phases of induction, outgrowth, and sculpting. Induction begins with signaling cues that specify organ primordia from germ layers, often involving diffusible factors like BMPs and Wnts that pattern tissues along embryonic axes. Outgrowth follows, driven by localized cell proliferation and migration, expanding the primordium into a rudimentary organ shape. Sculpting then refines this structure through morphogenetic movements, such as invagination, evagination, and looping, to achieve functional architecture. For instance, in vertebrate embryos, heart looping exemplifies sculpting, where left-right asymmetric signals from nodal flow and Pitx2 expression direct the linear heart tube to bend rightward, positioning chambers for septation and valve formation.^[96] Tissue interactions are central to coordinating these phases, particularly mesenchymal-epithelial signaling that patterns organ domains. In limb development, the apical ectodermal ridge (AER) secretes fibroblast growth factors (FGFs), such as FGF8 and FGF10, to maintain mesenchymal proliferation and outgrowth along the proximal-distal axis, while the zone of polarizing activity (ZPA) provides Sonic hedgehog (Shh) for anterior-posterior patterning. These reciprocal signals ensure progressive elaboration of skeletal elements and digits, with disruptions leading to truncated limbs. Genetic controls from early embryonic axes, including Hox gene expression, initiate induction by defining the limb field. Branching morphogenesis, as seen in lung development, serves as a sub-process during outgrowth and sculpting to generate alveolar structures.^[97]^[98]^[99] Scaling mechanisms maintain proportional organ size relative to the body through allometric growth, where organ dimensions adjust dynamically to embryonic size variations. In Drosophila, the heart scales isometrically with embryo length via uniform cell addition, while the visceral mesoderm exhibits hyperallometric growth to match body expansion, regulated by local insulin signaling and mechanical feedback. This ensures functional organ-body harmony, preventing mismatches in circulation or digestion. In vertebrates, similar principles apply, with liver and kidney growth calibrated by Hippo pathway effectors like Yap to achieve adult proportions.^[100]^[101] Across kingdoms, conserved polarity cues guide organ formation; in plants, apical-basal polarity in Arabidopsis embryogenesis, mediated by auxin gradients and PIN proteins, orients cell divisions in primordia to establish shoot-root axes. This polarity persists post-embryogenesis, directing vascular and epidermal differentiation in leaves and roots. Recent 2024 advances in C. elegans leverage real-time 4D imaging and automated segmentation to map over 95% of embryonic cells, uncovering how invariant organ shapes arise from consistent cell volumes, contacts, and Notch-mediated asymmetries in pharynx and intestine formation. These tools reveal robustness mechanisms, such as lag-1 and pop-1 regulation, ensuring organ invariance despite perturbations.^[102]^[103]^[87]^[104]

Pathological Morphogenesis

Morphogenesis in Cancer

Morphogenesis in cancer involves the dysregulation of developmental programs that drive tumor architecture, invasion, and metastasis, often mimicking epithelial-to-mesenchymal transition (EMT) and collective cell movements observed in normal embryogenesis.^[105] In epithelial tumors such as adenocarcinomas, cancer cells form gland-like structures and invasive strands through partial EMT, where cells retain some epithelial junctions while gaining migratory capabilities, enabling collective invasion into surrounding tissues.^[106] This process parallels normal branching morphogenesis but becomes aberrant, leading to disorganized tumor outgrowths that facilitate local spread and distant metastasis.^[107] Key pathways underlying tumor morphogenesis include Twist1-mediated EMT, which reprograms epithelial cells to a mesenchymal state, promoting motility and stem-like properties essential for invasion.^[108] Twist1 overexpression in breast and other cancers induces the loss of E-cadherin and upregulation of vimentin, driving collective cell migration while maintaining cell-cell contacts for coordinated invasion.^[109] Complementing this, matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, degrade the extracellular matrix (ECM) to create paths for tumor cell penetration, with MMP activity upregulated in response to EMT signals.^[110] These proteases not only facilitate physical invasion but also release bioactive ECM fragments that further stimulate tumor progression.^[111] Mechanical alterations in the tumor microenvironment exacerbate morphogenetic dysregulation, as stiffened ECM—resulting from increased collagen deposition and crosslinking—promotes branching-like tumor sprouts and invasive protrusions.^[112] Elevated matrix stiffness activates mechanosensitive pathways in cancer cells, enhancing contractility and directing sprout formation akin to vascular or ductal branching in development.^[113] A representative example is ductal carcinoma in situ (DCIS) in breast cancer, where aberrant branching morphogenesis leads to irregular ductal architectures confined by the basement membrane, often progressing to invasive lesions through disrupted polarity and excessive sprouting.^[114] Therapeutic strategies targeting these morphogenetic signals show promise, particularly inhibitors of YAP/TAZ signaling, which links ECM stiffness and fibrosis to cancer invasion.^[115] In 2025, novel YAP-TEAD inhibitors have demonstrated efficacy in preclinical models by attenuating fibrosis-driven ECM remodeling and reducing tumor branching in fibrotic cancers like hepatocellular carcinoma, highlighting their potential to disrupt pathological morphogenesis without broadly impairing normal tissue development.^[115]

Viral Morphogenesis

Viral morphogenesis refers to the ordered assembly of viral components into mature, infectious particles, primarily driven by interactions between viral structural proteins and host cellular machinery within infected cells.^[116] This process occurs in distinct stages, beginning with the formation of the nucleocapsid, where viral coat proteins encapsulate the genomic material to protect it and facilitate delivery.^[117] For many viruses, including retroviruses like HIV-1, the Gag polyprotein plays a central role in nucleocapsid self-assembly; multiple Gag molecules oligomerize at the plasma membrane, forming a spherical lattice around the RNA genome through interactions involving matrix, capsid, and nucleocapsid domains.^[118] This initial assembly yields an immature virion, which requires subsequent maturation for infectivity.^[119] Envelopment follows nucleocapsid formation in enveloped viruses, where the nucleocapsid acquires a lipid bilayer derived from host membranes studded with viral glycoproteins.^[116] Maturation typically involves proteolytic cleavage of polyproteins by viral proteases, inducing conformational rearrangements that stabilize the capsid and activate envelope functions; in HIV-1, cleavage of Gag by the viral protease rearranges the lattice from a spherical to a conical morphology, essential for uncoating in target cells.^[119] Structural proteins dictate capsid architecture, with icosahedral symmetry prevalent in many non-enveloped viruses, achieved through quasi-equivalent bonding of identical subunits into hexagonal lattices punctuated by pentamers that introduce curvature for closure.^[120] This Caspar-Klug model explains how subunit flexibility accommodates the geometric constraints of icosahedral shells, as seen in adenoviruses and picornaviruses.^[121] Host cell dependencies are critical, particularly for nuclear-replicating viruses like herpesviruses, which assemble nucleocapsids in the nucleus but require export to the cytoplasm for envelopment.^[122] In herpes simplex virus, nuclear egress involves the nuclear egress complex (pUL31/pUL34), which induces budding of capsids through the inner nuclear membrane, forming enveloped perinuclear virions that fuse with the outer nuclear membrane for release into the cytoplasm, followed by secondary envelopment at cytoplasmic vesicles.^[123] For coronaviruses, morphogenesis relies on membrane budding in the endoplasmic reticulum-Golgi intermediate compartment; the viral membrane protein M drives curvature and scission, incorporating nucleocapsids and spike proteins into vesicles that traffic to the plasma membrane for exocytosis.^[124] Assembly kinetics are governed by energy landscapes featuring multiple minima corresponding to oligomeric intermediates, with kinetic barriers influencing pathway efficiency; coarse-grained models reveal that capsid formation proceeds via a cascade of low-order associations, where dimer and pentamer formation precedes shell closure, as quantified in simulations of hepatitis B virus assembly with rate constants on the order of 10^6 M^{-1} s^{-1}.^[125] A representative example is bacteriophage T4, a complex double-stranded DNA virus, where tail fiber attachment completes head-tail morphogenesis; the six long tail fibers, composed of gp37 and gp38 proteins, assemble independently and attach to the tail tube via gp48 and gp54 baseplate proteins in a sequential, gene dosage-dependent process that ensures host receptor specificity.^[126] Genetic encoding of coat proteins, such as the major capsid protein in T4, directs these interactions through precise folding and multimerization signals.^[127] In oncogenic viruses like HPV, morphogenesis links to cellular dysregulation, but the core assembly remains protein-driven.^[116]

Morphogenesis in Regeneration

Regeneration in various organisms recapitulates key morphogenetic processes observed during embryogenesis, such as cell dedifferentiation, proliferation, and pattern formation, to restore lost or damaged tissues. In amphibians like salamanders, limb regeneration begins with the formation of a blastema, a proliferative mass of undifferentiated cells derived from local tissues through dedifferentiation, where mature cells revert to a progenitor-like state to repopulate the injury site. This process involves oriented cell divisions and signaling cues that guide the blastema's growth into a patterned appendage, mirroring embryonic limb development but activated post-injury.^[128] In planarians, flatworms renowned for their regenerative capacity, morphogenesis during regeneration relies on Wnt signaling to re-establish anterior-posterior polarity after injury. Upon bisection, Wnt ligands create a gradient that specifies posterior identity in the posterior fragment and suppresses it anteriorly, enabling the regeneration of a complete body plan from any cut piece. This polarity restoration involves chromatin modifications and beta-catenin-dependent transcriptional control, ensuring precise spatial organization of tissues.^[129] Mammalian regeneration, though more limited, exemplifies morphogenetic principles in organ repair, particularly in the liver, where hepatocyte proliferation restores mass after partial hepatectomy, accompanied by ductal morphogenesis to re-form biliary structures. Bipotent transitional liver progenitor cells, originating from biliary epithelial cells, contribute to hepatocyte replenishment during severe injury, involving epithelial plasticity and Notch-mediated fate decisions that parallel embryonic hepatogenesis. These shared pathways with embryogenesis, such as Wnt and Hedgehog signaling, highlight conserved mechanisms for tissue patterning in regenerative contexts.^[130]^[131] Recent bioengineering advances leverage computational tools to engineer regenerative morphogenesis, such as differentiable programming to control tissue folding in cell clusters. By integrating differentiable simulations with reinforcement learning, researchers design protocols that induce self-organized folding in engineered tissues, optimizing parameters for precise morphological outcomes and advancing applications in organoid development.^[132] A major challenge in mammalian regeneration is the propensity for scar formation, which disrupts regenerative morphogenesis by replacing functional tissue with fibrotic matrix, often due to inflammatory priming of fibroblasts that favors extracellular matrix deposition over progenitor activation. In contrast, scarless regeneration in models like fetal skin or certain adult tissues involves balanced immune responses and progenitor proliferation, underscoring the need to modulate these factors for therapeutic enhancement. Parallels to uncontrolled growth in cancer highlight risks in manipulating regenerative pathways, but adaptive repair remains the focus.^[133]

Modeling Approaches

Mathematical Models

Mathematical models provide analytical frameworks to predict and understand the dynamic processes underlying morphogenesis, focusing on differential equations and stability analyses that capture growth, pattern formation, and tissue dynamics. These models derive closed-form expressions for key phenomena, such as tissue expansion rates and pattern wavelengths, by minimizing energies or analyzing linear instabilities in reaction-diffusion systems. Seminal contributions emphasize theoretical derivations that link biophysical parameters to observable outcomes, enabling predictions without reliance on numerical iteration. A foundational approach to modeling tissue growth involves differential equations describing exponential expansion due to cell proliferation. The length L of a tissue segment evolves according to the equation \frac{dL}{dt} = \rho L, where \rho is the proliferation rate, leading to the solution L(t) = L_0 e^{\rho t}. This model captures the rapid, unconstrained growth phase in developing tissues, such as during early embryonic expansion, by assuming uniform cell division without spatial constraints.^[134] Vertex models formalize the mechanics of epithelial sheets by representing cells as polygons whose configurations minimize a total energy functional incorporating line tensions along cell boundaries. The energy is typically expressed as E = \sum_i \left( K_A (A_i - A_0)^2 + K_P (P_i - P_0)^2 \right) + \sum_j \Lambda_j l_j, where A_i and P_i are the area and perimeter of cell i, A_0 and P_0 are target values, K_A and K_P are stiffness coefficients, \Lambda_j is the tension of edge j, and l_j its length; dynamics follow force balance at vertices to evolve the sheet topology and shape. This framework derives tissue-level behaviors, such as apical constriction or sheet buckling, from local mechanical equilibria.^[135] Turing systems model pattern formation through reaction-diffusion equations for activator u and inhibitor v: \frac{\partial u}{\partial t} = D_u \nabla^2 u + f(u,v), \frac{\partial v}{\partial t} = D_v \nabla^2 v + g(u,v), where D_u < D_v enables instability of homogeneous states. Linear stability analysis around a steady state yields the dispersion relation from the eigenvalues \sigma of the matrix \begin{pmatrix} f_u - D_u k^2 & f_v \\ g_u & g_v - D_v k^2 \end{pmatrix}, given by \sigma = \frac{1}{2} \left[ \mathrm{tr} \pm \sqrt{\mathrm{tr}^2 - 4 \mathrm{det}} \right], with \mathrm{tr} = f_u + g_v - (D_u + D_v) k^2 and \mathrm{det} = (f_u - D_u k^2)(g_v - D_v k^2) - f_v g_u, for appropriate Jacobians f_u > 0, f_v < 0, g_u > 0, g_v < 0 (activator-inhibitor kinetics), ensuring stability without diffusion but instability with diffusion. The most unstable mode occurs at wave number k_c^2 \approx \frac{1}{2} \sqrt{\frac{f_u g_v - f_v g_u}{D_u D_v}} (exact form varies with approximations), yielding pattern wavelength \lambda \approx \frac{2\pi}{k_c}. This derivation predicts spatial scales in morphogenetic patterns, such as pigment stripes or digit spacing.^[15] Multicellular interactions are captured by phase-field approaches, which describe interface dynamics between cells or tissue phases using a continuous order parameter \phi(\mathbf{x},t) that varies smoothly from 1 inside a cell to 0 outside, governed by the Allen-Cahn equation \frac{\partial \phi}{\partial t} = -M \frac{\delta F}{\delta \phi} + \nabla \cdot (D \nabla \phi), where M is mobility, D is diffusion, and free energy F = \int \left[ \frac{\epsilon^2}{2} |\nabla \phi|^2 + W(\phi) \right] d\mathbf{x} with double-well potential W(\phi); for multiple cells, multiphase extensions sum over phase fields with coupling terms. These models derive interface motion laws, such as curvature-driven flow, to predict collective behaviors like tissue spreading or invagination.^[136] Validation of these models often involves comparing theoretical predictions to experimental observables, such as the periodicity of somite formation in vertebrate embryos, where clock-wavefront models predict somite spacing as the product of clock period T (typically 2-3 hours in mice) and wavefront speed v, yielding \lambda_s = v T \approx 100-200 \mu m per somite. Such derivations align with observed inter-somite distances across species, confirming the role of oscillatory dynamics in segmentation.^[137]

Computational Simulations

Computational simulations of morphogenesis employ numerical methods to replicate the dynamic processes of tissue formation, enabling researchers to explore emergent patterns from cellular interactions without physical experiments. These in silico approaches integrate biophysical principles, such as cell adhesion and mechanical forces, into algorithmic frameworks to model large-scale tissue behaviors. By simulating thousands of cells over time, they reveal how local rules scale to global morphologies, often validated against experimental data from embryonic development.^[138] Agent-based models, such as the Cellular Potts Model (CPM), treat individual cells as discrete agents governed by stochastic rules that drive emergent tissue shapes. In the CPM, cells are represented as lattices of spins, where energy minimization via Monte Carlo simulations incorporates parameters like differential adhesion energies between cell types, promoting phenomena such as cell sorting and tissue invagination during morphogenesis. For instance, this model has been used to simulate branching in lung development, where adhesion gradients lead to alveolar-like structures, highlighting how surface tension-like effects arise from collective cell behaviors. Seminal applications include modeling somitogenesis in zebrafish, where CPM captures oscillatory gene expression and mechanical feedback to form segmental patterns.^[139]^[140] Finite element methods (FEM) provide a continuum-based approach to simulate mechanical stresses in deforming tissues, discretizing embryonic structures into meshes to compute strain and force distributions during folding events. These models incorporate viscoelastic properties and active cellular contractions, allowing prediction of tissue buckling under compressive loads, as seen in neural tube closure where apical constriction generates bending moments. In simulations of Drosophila gastrulation, FEM reveals how yolk incompressibility influences ventral furrow invagination, with stress concentrations guiding cell rearrangements. This method excels in handling nonlinear deformations, offering insights into how mechanical feedback stabilizes morphogenetic outcomes across scales from single cells to whole organs.^[138]^[141] Recent integrations of machine learning, particularly differentiable programming, enable inverse design of morphogenetic processes by optimizing parameters for desired tissue architectures, such as 3D organoids. These models treat cell dynamics as differentiable functions, allowing gradient-based optimization of interaction rules and genetic circuits to achieve target shapes, like spherical clusters from initial cell aggregates. A 2024 framework demonstrated this by evolving rules for division, growth, and stress sensing in simulated cell populations, enabling directed axial elongation and growth homogenization in cell clusters.^[142] Such approaches accelerate discovery by screening vast parameter spaces, bridging simulation with experimental organoid engineering. In 2025, interdisciplinary models of brain folding integrated computational simulations with physical gel analogs to explore mechanisms of cortical pattern formation.^[143] High-throughput in silico screening of gene regulatory network (GRN) perturbations uses approximated expression trajectories to predict morphogenetic disruptions efficiently. By aligning static gene expression data with cell tracks from live imaging, these methods infer GRNs via stochastic differential equations and simulate perturbation effects, such as knocking out Wnt signaling to disrupt somite boundaries in zebrafish presomitic mesoderm. This allows rapid evaluation of thousands of genetic variants, identifying key regulators of pattern formation without exhaustive wet-lab testing, and has been applied to forecast defects in organoid patterning.^[144]^[145] A prominent example is the simulation of vascular network formation, where hybrid Cellular Potts Models incorporate chemotaxis and mechanical signaling to recapitulate endothelial cell sprouting and anastomosis. These models show that contact-inhibited migration along stiffness gradients in the extracellular matrix drives stable tube networks, with diffusion lengths around 70 µm matching in vitro observations of lacunae formation and branch remodeling. Such simulations falsify simpler hypotheses, like pure elongation, and underscore the role of cell-ECM interactions in angiogenesis during development.^[146]^[147]

References

[1]
Cellular mechanisms of morphogenesis - PMC - NIH
The reviews in this issue of Seminars in Cell and Developmental Biology highlight how progress in understanding processes of tissue generation, maintenance, and ...Missing: paper | Show results with:paper
[2]
Morphogenesis - Latest research and news - Nature
Morphogenesis is the process by which an organism, tissue or organ develops its shape. Morphogenesis is driven by various cellular and developmental processes.Missing: key facts
[3]
Tissue Morphogenesis Through Dynamic Cell and Matrix Interactions
Oct 16, 2023 · We review our understanding of matrix and adhesion molecules in tissue morphogenesis, with an emphasis on key physical interactions that drive ...
[4]
Morphogenesis | Embryo Project Encyclopedia
May 9, 2008 · The term morphogenesis generally refers to the processes by which order is created in the developing organism. This order is achieved as ...
[5]
Morphogenesis and Cell Adhesion - Developmental Biology - NCBI
Development involves not only the differentiation of cells, but also their organization into multicellular arrangements such as tissues and organs.
[6]
Caspar Friedrich Wolff (1734-1794) | Embryo Project Encyclopedia
Jul 7, 2009 · Caspar Friedrich Wolff is most famous for his 1759 doctoral dissertation, Theoria Generationis, in which he described embryonic development ...
[7]
Genetic Approaches to Study Tissue Morphogenesis in Drosophila
Morphogenesis is defined as the change of body shape over time, the understanding of which is one of the central questions of developmental biology.
[8]
The great small organisms of developmental genetics
C. elegans and Drosophila are very different invertebrate organisms with complementary strengths as models for Development.
[9]
Developmental genetics with model organisms - PubMed
Jul 26, 2022 · In Drosophila, a rich pattern is generated in the embryo as well as in adults that is used to unravel the underlying mechanisms of ...
[10]
Positional information and the spatial pattern of cellular differentiation
Cells which have their positional information specified with respect to the same set of points constitute a field. Positional information largely determines ...
[11]
Analysis of dynamic morphogen scale invariance - PubMed - NIH
Dec 6, 2009 · A number of conditions lead to scale invariance of the morphogen distribution at equilibrium and during the transient approach to equilibrium.
[12]
Caspar Friedrich Wolff's Theory of Epigenesis - jstor
In his dissertation, Wolff proposed a model for development in plants and animals based on two factors: the ability of plant and animal fluids to solidify, and ...
[13]
The revolutionary developmental biology of Wilhelm His, Sr - PMC
Feb 22, 2022 · In our view, His's growth law was the first comprehensive model of morphogenesis and morphological evolution with a testable mechanism. His ...
[14]
Morphogenesis one century after On Growth and Form | Development
Dec 1, 2017 · Morphogenesis, the study of how forms arise in biology, has attracted scientists for aeons. A century ago, D'Arcy Wentworth Thompson ...
[15]
The chemical basis of morphogenesis - Journals
The purpose of this paper is to discuss a possible mechanism by which the genes of a zygote may determine the anatomical structure of the resulting organism.
[16]
Hox genes, evo-devo, and the case of the ftz gene - PMC
The discovery of the broad conservation of embryonic regulatory genes across animal phyla, launched by the cloning of homeotic genes in the 1980s, ...
[17]
Morphogenesis: Setting the pace of embryo folding - ScienceDirect
Apr 8, 2024 · Tissue folding is a crucial process for shape change during embryonic morphogenesis. Folding allows simple tissues to be sculpted into more ...
[18]
Genetically-stable engineered optogenetic gene switches modulate ...
Dec 2, 2024 · Here, we implement blue and red light-responsive gene switches to engineer genomically stable two- and three-dimensional mammalian tissue models.
[19]
Gene regulatory networks - PNAS
Gene regulatory networks explicitly represent the causality of developmental processes. They explain exactly how genomic sequence encodes the regulation of ...Missing: review | Show results with:review
[20]
Constructing transcriptional regulatory networks
Here we review the properties of transcriptional regulatory networks and the rapidly evolving approaches that will enable the elucidation of their structure ...
[21]
A gene complex controlling segmentation in Drosophila - Nature
Dec 7, 1978 · The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal ...
[22]
Spatial Bistability Generates hunchback Expression Sharpness in ...
Sep 26, 2008 · Analysis of our model indicates that the Hb sharpness can be produced by spatial bistability, in which hb self-regulation produces two stable levels of ...Missing: loops | Show results with:loops
[23]
Hedgehog signaling in animal development: paradigms and principles
The first important breakthrough in unraveling how segment-polarity genes act came in the mid-1980s with the cloning of two members of the class, wingless and ...
[24]
Evolutionary conservation and divergence of the segmentation ...
Apr 17, 2007 · The role of the lowest level of the segmentation gene cascade, the segment-polarity gene network, appears to be the most conserved. The segment- ...
[25]
Quantitative Models of Developmental Pattern Formation
We discuss how models can be used to test the feasibility of proposed patterning mechanisms and characterize their systems-level properties.Main Text · Analyzing Models · Acknowledgments
[26]
On the Use of the Hill Functions in Mathematical Models of Gene ...
Hill functions follow from the equilibrium state of the reaction in which n ligands simul- taneously bind a single receptor. This result if often employed to ...
[27]
Signaling in Cell Differentiation and Morphogenesis - PubMed Central
In this article, I review some of the signaling pathways that play essential roles during embryonic development. These examples show some of the mechanisms ...Missing: authoritative | Show results with:authoritative
[28]
Wnt Signaling in Vertebrate Axis Specification - PubMed Central - NIH
The Wnt pathway is a major embryonic signaling pathway that controls cell proliferation, cell fate, and body-axis determination in vertebrate embryos.
[29]
Canonical and Non-Canonical Wnt Signaling Generates Molecular ...
Aug 2, 2024 · This review discusses the regulatory roles of Wnt pathway components in embryonic axis formation by focusing on vertebrate models.
[30]
Wnt/β-catenin signaling is an evolutionarily conserved determinant ...
May 26, 2020 · The role of Wnt/β-catenin signaling in the dorsal/ventral (DV) axis establishment was first demonstrated in Xenopus by gain-of-function ...Missing: seminal | Show results with:seminal
[31]
Understanding the Principles of Pattern Formation Driven by Notch ...
In this section, we review experimental systems that exemplify two well-known patterning mechanisms enabled by Notch signaling: lateral inhibition and lateral ...
[32]
Notch-mediated lateral inhibition regulates proneural wave ... - PNAS
Aug 17, 2016 · Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt and pepper patterns during various developmental processes.
[33]
Notch signaling pathway: architecture, disease, and therapeutics
Mar 24, 2022 · Inhibiting NOTCH signaling increases the differentiation of secretory goblet cells. Additionally, the lateral inhibition of NOTCH/DLL1 ...
[34]
BMP Signaling: Lighting up the Way for Embryonic Dorsoventral ...
It is well-known that the morphogen gradient created by BMP signaling activity is crucial for DV axis patterning across a diverse set of vertebrates.
[35]
TGF-β Family Signaling in Early Vertebrate Development - PMC
Bone morphogenetic protein (BMP) signaling patterns tissues along the dorsal–ventral axis and simultaneously directs the cell movements of convergence and ...
[36]
TGFβ family signaling and development
Mar 12, 2021 · The cell fates of animal embryos are patterned along the dorsoventral (DV) axis. Increasing evidence suggests that R-Smad-dependent BMP ...Non-canonical (Smad... · Bmp and Nodal signaling in... · TGFβ family signaling in...
[37]
Pattern formation in the vertebrate neural tube: a sonic hedgehog ...
Aug 1, 2008 · In ventral regions of the presumptive spinal cord, the secreted molecule sonic hedgehog (Shh) acts as a long-range morphogen(Box 1) that directs ...
[38]
Establishing Hedgehog Gradients during Neural Development - PMC
Sonic Hedgehog (Shh) is one of the most important morphogens that displays pleiotropic functions during embryonic development, ranging from neuronal patterning ...
[39]
Precision of morphogen gradients in neural tube development - Nature
Mar 3, 2022 · In the French flag model, domain boundaries ... Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism.
[40]
Modulation of Phase Shift between Wnt and Notch Signaling ...
Feb 22, 2018 · We provide functional evidence that the oscillation phase shift between Wnt and Notch signaling is critical for PSM segmentation.
[41]
The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the ...
In this paper we focus on interactions between the canonical Wnt ... Notch and Wnt signaling pathways and the crosstalk between them during somitogenesis.
[42]
Mathematical models for the Notch and Wnt signaling pathways and ...
Apr 20, 2013 · These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived ...
[43]
The roles of FGFs in the early development of vertebrate limbs
Several lines of evidence suggest that FGF genes, particularlyFgf8 and Fgf10, play a role in mediating the initial outgrowth of the limb and in establishing the ...
[44]
Establishing the pattern of the vertebrate limb | Development
Sep 11, 2020 · Initial outgrowth of the limb is driven by the Fgf10-Fgf8 feedback loop that operates between the mesoderm (blue) and overlying apical ...Limb polarity · Limb bud initiation · Limb pattern specification · Limb growth
[45]
Limb Development - FGF Signalling in Vertebrate Development - NCBI
Two key signalling centres drive vertebrate limb development: the apical ectodermal ridge (AER) and the zone of polarising activity (ZPA).
[46]
Adherens junctions: from molecules to morphogenesis - Nature
Adherens junctions (AJs) meet the dual challenge of maintaining tissue architecture and facilitating cell movement during tissue development and renewal.
[47]
A short guide to the tight junction | Journal of Cell Science
May 7, 2024 · The term 'occludens' refers to the ability of TJs to occlude (that is, close or seal) the intercellular space, as seen in transmission electron ...
[48]
Structure, Function and Regulation of Desmosomes - PMC
Desmosomes are adhesive intercellular junctions that mechanically integrate adjacent cells by coupling adhesive interactions mediated by desmosomal cadherins.
[49]
The E-Cadherin and N-Cadherin Switch in Epithelial-to ... - NIH
N-cadherin is upregulated while E-cadherin is downregulated during EMT in cancers and this “cadherin switch” is associated with enhanced migratory and invasive ...
[50]
Ideal, catch, and slip bonds in cadherin adhesion - PMC - NIH
Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in ...
[51]
Cadherin-dependent differential cell adhesion in Xenopus causes ...
Our results show that gastrulation is surprisingly tolerant of overall changes in adhesion. Also, as expected, experimentally generated, cadherin-based adhesion ...<|control11|><|separator|>
[52]
The Wnt signaling pathways and cell adhesion - PubMed
Jan 1, 2012 · The Wnt pathways regulate morphogenesis by controlling cell adhesion and migration; processes that when corrupted, lead to tumorgenesis.
[53]
The Extracellular Matrix In Development and Morphogenesis
This review considers the range of cell and tissue functions attributed to ECM molecules and summarizes recent findings specific to key developmental processes.
[54]
Endothelial Extracellular Matrix | Circulation Research
A major message from these studies is that laminins are the primary determinants of basement membrane assembly and that other basement membrane components such ...
[55]
Focal adhesion-mediated cell anchoring and migration: from in vitro ...
May 19, 2022 · This adhesion is mediated by integrins, which form a bridge between the extracellular matrix (ECM) outside the cell and the actomyosin network ...Introduction · Force transmission and... · Focal adhesions anchor cells...
[56]
How the extracellular matrix shapes neural development - Journals
Jan 9, 2019 · In this review, we will discuss how the ECM shapes neural development, focusing on how it regulates aspects such as cell proliferation, differentiation, ...
[57]
Dynamic 3D Cell Rearrangements Guided by a Fibronectin Matrix ...
Oct 15, 2009 · Using 3D and 4D imaging of somite formation we discovered that somitogenesis consists of a complex choreography of individual cell movements.
[58]
Integrin α5 is required for somite rotation and boundary formation in ...
Aug 8, 2007 · These data demonstrate that the role of integrin α5 in somite boundary formation is conserved in a species using a unique mechanism of somitogenesis.
[59]
The pulse of morphogenesis: actomyosin dynamics and regulation ...
Sep 2, 2020 · Here, we summarize our current understanding of actomyosin networks and tissue-generated contractile forces based on recent work in the field.Missing: velocity | Show results with:velocity
[60]
Pulsed contractions of an actin–myosin network drive apical constriction - Nature
### Summary of Pulsatile Contractility Mechanism in Apical Constriction During Drosophila Ventral Furrow Invagination
[61]
Regulation of mitotic spindle orientation: an integrated view | EMBO reports
Summary of each segment:
[62]
Review Cell migration during morphogenesis - ScienceDirect.com
May 1, 2010 · Neural crest cells stop migrating in areas where repulsive signals are low. For example, trunk neural crest cells migrate away from the neural ...
[63]
Collective cell migration in morphogenesis, regeneration and cancer
The collective migration of cells as a cohesive group is a hallmark of the tissue remodelling events that underlie embryonic morphogenesis, wound repair and ...<|control11|><|separator|>
[64]
Neural Crest Migration Orchestrated by Molecular and Mechanical ...
Oct 1, 2025 · Neural crest cells migrate collectively in subpopulations, ranging in size from streams with hundreds of cells delaminating in the cephalic ...
[65]
Review Gastrulation Movements: the Logic and the Nuts and Bolts
Cell intercalation in a dorso-ventral direction lengthens the germ band and pushes its posterior end onto the dorsal side. The invaginated mesodermal tube ...Missing: evagination | Show results with:evagination
[66]
Cellular systems for epithelial invagination - Journals
Mar 27, 2017 · Epithelial bending is self-evidently a multicellular process in which multiple connected cells coordinate their behaviours to change the shape of the tissue.
[67]
Guidance Mechanisms in Solitary and Collective Cell Migration
Jan 18, 2011 · This perspective discusses the relationship between guidance input and the cellular output, considering effects from classical chemotaxis to contact-dependent ...
[68]
VEGF guides angiogenic sprouting utilizing endothelial tip cell ...
We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated ...
[69]
Velocity Fields in a Collectively Migrating Epithelium - PMC - NIH
We report quantitative measurements of the velocity field of collectively migrating cells in a motile epithelium.
[70]
Movement Directionality in Collective Migration of Germ Layer ...
Jan 26, 2010 · Here we determine how movement directionality is established in collective mesendoderm migration during zebrafish gastrulation.
[71]
Quantifying mechanical forces during vertebrate morphogenesis
Jul 5, 2024 · Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these ...
[72]
Patterned invagination prevents mechanical instability during ...
Sep 3, 2025 · Here we show that an evolutionary novelty of fly embryos—the patterned embryonic invagination known as the cephalic furrow—has a mechanical role ...
[73]
Mechanobiology of YAP and TAZ in physiology and disease - PMC
YAP and TAZ mechanotransduction is critical for driving stem cell behaviour and regeneration, and sheds new light on the mechanisms by which aberrant cell ...
[74]
Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway
The Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis.
[75]
Viscoelasticity during development: What is it? and why should you ...
Sep 27, 2025 · These tunable viscoelastic properties allow cells and tissues to resist applied loads and transmit force to neighboring cells and the ...
[76]
A mechanical wave travels along a genetic guide to drive the ...
We study the formation of the cephalic furrow, a fold that runs along the embryo dorsal-ventral axis during Drosophila gastrulation and the developmental role ...
[77]
Traction force microscopy with optimized regularization and ... - Nature
Jan 24, 2019 · Traction force microscopy (TFM) is a versatile and perturbation-free method yielding a spatial image of the stress exerted by cells on ...
[78]
Revisiting the relationship between turgor pressure and plant cell ...
Dec 16, 2022 · Numerous theoretical and experimental studies suggest that turgor pressure can be both spatially inhomogeneous and actively modulated during morphogenesis.
[79]
Coordination of plant cell division and expansion in a simple ... - PNAS
Plant cell expansion is believed to result from turgor pressure acting as a driving force on a yielding cell wall, where these factors are controlled by the ...
[80]
Turing's theory of morphogenesis of 1952 and the subsequent ... - NIH
Feb 8, 2012 · In his pioneering work, Alan Turing showed that de novo pattern formation is possible if two substances interact that differ in their diffusion range.
[81]
Biologists Home In on Turing Patterns - Quanta Magazine
Mar 25, 2013 · For example, experiments with zebra fish stripes have shown that they arise from a Turing mechanism, but rather than secreting chemicals that ...
[82]
Different types of oscillations in Notch and Fgf signaling regulate the ...
These results suggest that Notch oscillators define the prospective somite region, while Fgf oscillators regulate the pace of segmentation. Keywords.
[83]
Delta-Notch signalling in segmentation - PMC - PubMed Central
Delta-Notch signalling a primary role within the segmentation clock as a means of synchronizing noisy, oscillating cells to a common local rhythm.
[84]
On Buckling Morphogenesis - PMC - PubMed Central - NIH
These mechanical instabilities cause essentially one-dimensional epithelial tubes and two-dimensional epithelial sheets to buckle or wrinkle into complex ...
[85]
The developmental mechanics of divergent buckling patterns in the ...
Jul 5, 2024 · We study the link between differential mechanical properties and the morphogenesis of distinct anteroposterior compartments in the intestinal tract.
[86]
Cell lineage-resolved embryonic morphological map reveals ...
Apr 18, 2025 · Here we present a comprehensive real-time cellular map that covers over 95% of the cells formed during Caenorhabditis elegans embryogenesis.
[87]
Lineage-resolved analysis of embryonic gene expression ... - Science
Jun 19, 2025 · The conserved invariant embryonic lineage of Caenorhabditis elegans and C. briggsae makes them ideal for comparing cell type gene expression ...
[88]
Auxin influx carriers stabilize phyllotactic patterning - PubMed Central
This mechanism generates the spacing between neighboring primordia, which results in regular phyllotaxis. Studies of the role of auxin transport in phyllotactic ...
[89]
Phyllotaxis involves auxin drainage through leaf primordia
Jun 1, 2015 · Models of phyllotaxis invoke the accumulation of auxin at leaf initials and removal of auxin through their developing vascular strand, the ...
[90]
https://journals.biologists.com/dev/article/142/11/1992/46778/Phyllotaxis-involves-auxin-drainage-through-leaf
[91]
Genetic Regulation of Branching Morphogenesis: Lessons Learned ...
Oct 1, 2003 · With continued epithelial proliferation, the submandibular gland primordium becomes a solid, elongated epithelial stalk that forms lateral and ...
[92]
Identification of genes involved in VEGF-mediated vascular ... - Nature
Jun 28, 2004 · Furthermore, our analysis of the VEGF-null CEB suggests that VEGF expression is necessary for EC branching and morphogenesis.
[93]
Getting to the Heart of Left–Right Asymmetry: Contributions ... - NIH
Jun 4, 2021 · In this review, we will discuss how left–right asymmetry is established and how that influences subsequent asymmetric development of the early embryonic heart.Missing: outgrowth sculpting
[94]
Epithelial mesenchymal interactions, the ECM and limb development
In this review, I will touch upon recent evidence, illustrated by examples of FGF signalling in vertebrate limb development.
[95]
Fibroblast Growth Factor 10 and Vertebrate Limb Development
Jan 6, 2019 · FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis. Development 135, 483–491 ...
[96]
Next generation limb development and evolution: old questions ...
Nov 15, 2015 · This Review focuses on the insights these studies have given into the gene regulatory networks that govern limb development and into the fin-to-limb transition.
[97]
Scaling of internal organs during Drosophila embryonic development
Our work shows that internal organs can adapt to embryo size changes in Drosophila, but the extent to which they scale varies significantly between organs.
[98]
Network‐regulated organ allometry: The developmental regulation ...
Jun 21, 2020 · Morphological scaling relationships, or allometries, describe how traits grow coordinately and covary among individuals in a population.
[99]
Apical–basal pattern formation in Arabidopsis embryogenesis
The apical-basal pattern includes the shoot meristem, cotyledons, hypocotyl, radicle, and root meristem, along with the radial pattern of tissue layers.
[100]
Polarity and signalling in plant embryogenesis - Oxford Academic
The observed apical‐basal polarity in the zygote of Arabidopsis and Fucus presages polar development during embryogenesis. In each species, the zygote undergoes ...
[101]
Automated profiling of gene function during embryonic development
Jun 6, 2024 · We used 4D imaging of C. elegans embryogenesis to capture the effects of 500 gene knockdowns and developed an automated approach to compare developmental ...
[102]
An emerging tumor invasion mechanism about the collective cell ...
There are a series of cell-cell junction mechanisms that have been involved in tumor collective cell invasion. Epithelial tumors metastasis majorly referred to ...
[103]
Collective cell migration modes in development, tissue repair and ...
Jun 5, 2025 · In this Review, we describe the elegant mechanisms used by collectively migrating cells in vivo to coordinate their movements and obtain directional ...
[104]
Hijacking a Morphogenesis Proteinase for Cancer Cell Invasion
Oct 22, 2018 · A long-standing question in biology is whether cancer cells exploit developmental processes to invade the surrounding stroma.
[105]
Unraveling the TWIST between EMT and Cancer Stemness
Jan 8, 2015 · Twist1 has a well-established role in inducing Epithelial-Mesenchymal Transition (EMT) to promote tumor invasion and metastasis and can also ...
[106]
Molecular mechanisms of TWIST1‐regulated transcription in EMT ...
Sep 8, 2023 · Non‐acetylated TWIST1 induces EMT and metastasis by interacting with the NuRD complex to repress epithelial genes.
[107]
Matrix Metalloproteinases in Cancer Cell Invasion - NCBI - NIH
In this chapter, we discuss the role of MMPs and their inhibitors in tumor cell invasion as a basis for prognostication and targeted therapeutic intervention.
[108]
MMP proteolytic activity regulates cancer invasiveness by ... - Nature
Oct 27, 2017 · Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby ...
[109]
Extracellular matrix and its therapeutic potential for cancer treatment
Apr 23, 2021 · In turn, a stiffened ECM accelerates the growth of tumor cells. Such communication between cancer cells and fibroblasts forms a positive loop ...
[110]
Matrix stiffening promotes a tumor vasculature phenotype - PNAS
Dec 29, 2016 · We show that the stiffness of the underlying extracellular matrix also plays a central role in promoting angiogenesis and a characteristic tumor-like ...
[111]
Harnessing 3D models of mammary epithelial morphogenesis ... - NIH
Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease.
[112]
Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates ...
Aug 2, 2025 · YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells.
[113]
Virus Morphology, Replication, and Assembly - PMC - PubMed Central
In this chapter, I will discuss aspects of viral morphology, the mode of viral replication, and viral morphogenesis.
[114]
Virus Morphogenesis - an overview | ScienceDirect Topics
Morphogenesis and Release. During viral morphogenesis, nucleocapsids start forming in the nuclear virogenic stroma, first by the production of capsid sheaths ...
[115]
In Vitro Assembly Properties of Human Immunodeficiency Virus ...
In summary, we have shown that HIV-1 Gag polyprotein is capable of self-assembly into regular, ordered structures. This assembly process requires the ...<|separator|>
[116]
High-resolution structures of HIV-1 Gag cleavage mutants determine ...
Sep 14, 2018 · HIV-1 maturation occurs via multiple proteolytic cleavages of the Gag polyprotein, causing rearrangement of the virus particle required for ...
[117]
Origin of icosahedral symmetry in viruses - PNAS
The shells (capsids) of sphere-like viruses have the symmetry of an icosahedron and are composed of coat proteins (subunits) assembled in special motifs, the T ...
[118]
Models of viral capsid symmetry as a driver of discovery in virology ...
Feb 2, 2021 · Such models can be built by drawing an icosahedral net on a hexagonal lattice and then folding this net up into an icosahedron. In their seminal ...
[119]
Comprehensive analysis of nuclear export of herpes simplex virus ...
Morphogenesis of herpesviral virions is initiated in the nucleus but completed in the cytoplasm. Mature virions contain more than 25 tegument proteins many ...
[120]
Structure of a herpesvirus nuclear egress complex subunit reveals ...
Herpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple ...
[121]
Structure of SARS-CoV-2 membrane protein essential for virus ...
Aug 5, 2022 · The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and ...
[122]
Model-Based Analysis of Assembly Kinetics for Virus Capsids or ...
We have developed a model of capsid assembly, based on a cascade of low-order reactions, that allows us to calculate kinetic simulations.
[123]
Intracellular morphogenesis of bacteriophage T4 I. Gene dosage ...
Intracellular morphogenesis of bacteriophage T4 I. Gene dosage effects on early functions and tail fiber assembly.
[124]
Structure and morphogenesis of bacteriophage T4 - PubMed
The fibers and the tail carry the host cell recognition sensors and are required for attachment of the phage to the cell surface. The tail also serves as a ...
[125]
Molecular basis of positional memory in limb regeneration - Nature
May 21, 2025 · The amputation of a salamander limb triggers anterior and posterior connective tissue cells to form distinct signalling centres that ...
[126]
Wnt/β-catenin signalling is required for pole-specific chromatin ...
Jan 18, 2023 · Silencing of notum or wnt1 during planarian regeneration produces a shift in polarity, giving rise to anterior tails in notum (RNAi) animals and ...
[127]
Molecular mechanisms in liver repair and regeneration - Nature
Feb 8, 2025 · Numerous signaling pathways significantly contribute to liver repair and regeneration, facilitating hepatocyte proliferation and non-parenchymal ...
[128]
Bipotent transitional liver progenitor cells contribute to liver ... - Nature
Mar 13, 2023 · Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe ...
[129]
Engineering morphogenesis of cell clusters with differentiable ...
Aug 13, 2025 · Engineering morphogenesis of cell clusters with differentiable programming · Abstract · Main · Results · Discussion · Methods · Data availability.
[130]
Comparative regenerative mechanisms across different mammalian ...
Feb 23, 2018 · Collagen I in the scar inhibits hepatocyte proliferation and must be degraded by MMPs released by hepatic macrophages, before laminin deposition ...
[131]
Modeling proliferative tissue growth: A general approach and an ...
Sep 16, 2008 · The elongation and radial expansion can both be described by exponential growth. The growth rates for the case study can be interpreted in terms ...
[132]
Vertex models: from cell mechanics to tissue morphogenesis
Mar 27, 2017 · We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions.
[133]
MorphoSim: an efficient and scalable phase-field framework for ...
Feb 17, 2023 · The phase field model can accurately simulate the evolution of microstructures with complex morphologies, and it has been widely used for ...
[134]
Mathematical Models for Somite Formation - PMC - NIH
Mathematical models for somite formation include the Clock and Wavefront model, models for the segmentation clock, FGF8 gradient, and models for cell adhesion.
[135]
Computational Models for Mechanics of Morphogenesis - PMC
In this review, we first give an overview of fundamental mechanical theories for morphogenesis, and then focus on models for specific processes.
[136]
Cellular Potts modeling of complex multicellular behaviors in tissue ...
Jun 8, 2017 · We review the cellular Potts model in tissue morphogenesis, and discuss its usability for modeling complex developmental phenomena by ...Missing: seminal | Show results with:seminal
[137]
From energy to cellular forces in the Cellular Potts Model - NIH
The Cellular Potts Model (CPM) is a convenient and relatively popular computational platform for modeling dynamic, irregular and highly fluctuating cell shapes ...Missing: seminal | Show results with:seminal
[138]
Embryonic Tissue Morphogenesis Modeled by FEM | J. Biomech Eng.
A three-dimensional, large-strain finite element formulation for the simulation of morphogenetic behaviors in embryonic tissues is presented.
[139]
Approximated gene expression trajectories for gene regulatory ...
Sep 20, 2024 · Here we present a methodology to reverse-engineer GRNs underlying pattern formation in tissues that are undergoing morphogenetic changes such as ...
[140]
A computational dynamic systems model for in silico prediction of ...
Dec 18, 2024 · Simulates mammalian neural tube closure using cell signaling and biomechanics. Predicts both the nature and probability of defects from genetic perturbations.
[141]
Falsifying computational models of endothelial cell network ...
In this study, we analysed time-lapse videos of endothelial cell network formation and compared these with three computational models.
[142]
Cell-based computational modeling of vascular morphogenesis ...
Here, we present a step-by-step, practical tutorial for building cell-based simulations of vascular morphogenesis using the Tissue Simulation Toolkit (TST). The ...