Developmental Biology

🐣Developmental Biology Unit 7 – Cell Migration and Morphogenesis

Cell migration and morphogenesis are crucial processes in developmental biology. They involve the movement of cells and the shaping of tissues, playing key roles in gastrulation, organ formation, and wound healing. These processes rely on complex interactions between cells and their environment. Understanding cell migration and morphogenesis requires knowledge of cellular mechanisms, molecular players, and signaling pathways. Key concepts include cell polarity, cytoskeletal dynamics, and extracellular matrix interactions. Techniques like live cell imaging and in vitro assays help researchers study these fascinating biological phenomena.

Key Concepts in Cell Migration and Morphogenesis

  • Cell migration plays a crucial role in various developmental processes (gastrulation, neural crest migration, wound healing)
  • Morphogenesis the process by which tissues and organs develop their shape and structure through coordinated cell movements and rearrangements
  • Cell migration can be individual (mesenchymal) or collective (epithelial sheets)
    • Individual migration cells move independently of each other
    • Collective migration cells maintain cell-cell contacts and move as a cohesive group
  • Cell polarity establishment of asymmetry within a cell, essential for directed migration
  • Cytoskeletal dynamics the reorganization of actin and microtubule networks drives cell shape changes and movement
  • Cell adhesion molecules (cadherins, integrins) mediate cell-cell and cell-matrix interactions during migration
  • Chemotaxis the directed movement of cells in response to chemical gradients (growth factors, chemokines)
  • Mechanotransduction the ability of cells to sense and respond to mechanical cues from their environment

Cellular Mechanisms Driving Movement

  • Actin polymerization drives the formation of protrusions (lamellipodia, filopodia) at the leading edge of migrating cells
  • Myosin II-mediated contraction generates force for cell body translocation and rear retraction
  • Focal adhesions dynamic structures that link the cytoskeleton to the extracellular matrix, providing traction for movement
  • Membrane trafficking (endocytosis, exocytosis) regulates the recycling of adhesion molecules and membrane dynamics during migration
  • Rho GTPases (Rho, Rac, Cdc42) key regulators of cytoskeletal dynamics and cell polarity
    • Rho promotes stress fiber formation and cell contractility
    • Rac stimulates lamellipodia formation and membrane ruffling
    • Cdc42 induces filopodia formation and establishes cell polarity
  • Microtubules provide structural support and facilitate intracellular transport during migration
  • Intermediate filaments contribute to cell mechanical stability and resistance to stress

Molecular Players and Signaling Pathways

  • Growth factors (EGF, FGF, VEGF) stimulate cell migration through receptor tyrosine kinase (RTK) signaling
  • Chemokines (CXCL12, CCL21) guide cell migration during development and immune responses
  • Integrins transmembrane receptors that mediate cell-matrix adhesion and activate intracellular signaling cascades
  • Cadherins calcium-dependent cell-cell adhesion molecules that maintain tissue integrity during collective migration
  • Wnt signaling pathway regulates cell polarity, migration, and morphogenetic movements (convergent extension)
  • TGF-β signaling pathway induces epithelial-mesenchymal transition (EMT) and promotes cell migration during development and cancer progression
  • Notch signaling pathway controls cell fate decisions and influences cell migration in various contexts (angiogenesis, neural crest migration)
  • Hippo signaling pathway regulates cell proliferation, survival, and migration through the transcriptional co-activators YAP/TAZ

Extracellular Matrix Interactions

  • Extracellular matrix (ECM) provides structural support and signaling cues for migrating cells
  • ECM composition (collagen, fibronectin, laminin) varies across tissues and developmental stages
  • Integrins mediate cell-ECM adhesion and transduce mechanical and chemical signals
    • Integrin activation leads to the formation of focal adhesions and activation of downstream signaling pathways (FAK, Src)
  • Matrix metalloproteinases (MMPs) degrade ECM components, facilitating cell invasion and remodeling
  • Heparan sulfate proteoglycans (HSPGs) bind growth factors and regulate their availability and signaling
  • Hyaluronan a glycosaminoglycan that influences cell migration and tissue hydration
  • Durotaxis the directed movement of cells towards regions of higher substrate stiffness
  • Contact guidance the alignment and migration of cells along ECM fibers or topographical features

Developmental Contexts and Examples

  • Gastrulation the formation of the three germ layers (ectoderm, mesoderm, endoderm) through coordinated cell movements (invagination, involution, epiboly)
  • Neural crest migration a highly migratory population of cells that give rise to various cell types (neurons, glia, melanocytes, craniofacial structures)
  • Angiogenesis the formation of new blood vessels from pre-existing ones, involves endothelial cell migration and tube formation
  • Wound healing the coordinated migration of keratinocytes, fibroblasts, and immune cells to close a wound and restore tissue integrity
  • Drosophila border cell migration a model system for studying collective cell migration during oogenesis
  • Zebrafish lateral line development involves the collective migration of a group of cells called the primordium
  • Xenopus convergent extension the narrowing and lengthening of the body axis during gastrulation, driven by polarized cell intercalation
  • Chick primitive streak formation the site of gastrulation in avian embryos, where epiblast cells undergo EMT and migrate to form the mesoderm and endoderm

Techniques for Studying Cell Migration

  • Live cell imaging allows the visualization of cell migration in real-time using fluorescent reporters and microscopy techniques (confocal, light sheet)
  • Cell tracking software enables the quantification of cell migration speed, directionality, and trajectory
  • In vitro assays (wound healing, transwell, microfluidic devices) provide controlled environments to study cell migration under specific conditions
  • In vivo lineage tracing using genetic labeling techniques (Cre-loxP, fluorescent proteins) to follow the fate and migration of specific cell populations
  • Optogenetics the use of light-sensitive proteins to control cell behavior and signaling pathways with spatial and temporal precision
  • Biomaterial scaffolds engineered matrices that mimic the physical and biochemical properties of the ECM to study cell migration in 3D environments
  • Traction force microscopy a technique that measures the forces exerted by migrating cells on their substrate
  • Atomic force microscopy (AFM) a high-resolution imaging technique that can also measure the mechanical properties of cells and tissues

Morphogenesis and Tissue Formation

  • Convergent extension a conserved morphogenetic process that elongates tissues through polarized cell intercalation
  • Branching morphogenesis the formation of branched structures (lungs, mammary glands, kidneys) through coordinated cell migration and proliferation
  • Epithelial folding the bending and invagination of epithelial sheets to create complex 3D structures (neural tube, optic cup)
  • Cell sorting the segregation of different cell types based on their differential adhesion properties
  • Planar cell polarity (PCP) the coordinated orientation of cells within the plane of an epithelium, essential for directed cell migration and tissue organization
  • Mechanically-driven morphogenesis the shaping of tissues through the generation and transmission of mechanical forces (tension, compression)
  • Tissue fusion the merging of two separate tissue layers or structures to form a continuous unit (palate, heart)
  • Organoids self-organizing 3D cell cultures that recapitulate the structure and function of mini-organs, useful for studying morphogenesis and disease modeling

Clinical Implications and Future Directions

  • Cancer metastasis the spread of cancer cells from the primary tumor to distant sites, involves cell migration and invasion
    • Targeting cell migration pathways (Rho GTPases, FAK, MMPs) is a promising strategy for anti-metastatic therapies
  • Wound healing disorders (chronic wounds, fibrosis) result from impaired cell migration and tissue repair
  • Regenerative medicine harnessing the migratory and morphogenetic potential of stem cells to regenerate damaged or lost tissues
  • Organ-on-a-chip microfluidic devices that mimic the structure and function of human organs, enabling the study of cell migration and drug screening
  • Single-cell sequencing technologies provide high-resolution insights into the molecular heterogeneity of migrating cell populations
  • Computational modeling integration of experimental data with mathematical models to predict and simulate cell migration and morphogenesis
  • Biomaterials and tissue engineering designing synthetic matrices and scaffolds that guide cell migration and tissue formation for regenerative applications
  • Gene editing (CRISPR-Cas9) a powerful tool for dissecting the genetic basis of cell migration and morphogenesis, and for developing targeted therapies


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© 2024 Fiveable Inc. All rights reserved.
AP® and SAT® are trademarks registered by the College Board, which is not affiliated with, and does not endorse this website.