Unformatted text preview: BICD 130 Embryos, Genes, and Development MORPHOGENESIS Establishment of form and position in the developing organism: Rearrangement of cell positions relative to one another Shaping and alignment of individual cells Processes Underlying Morphogenesis Cell division (direction and number) Cell shape changes Cell state transitions (epithelium/mesenchyme) Cell migration Cell growth Cell death Cell surface and extracellular matrix changes Morphogenesis and Cell Adhesion Morphogenesis at two levels: Expression of individual cell structure and shape (cytoskeleton) Organization of cell groups into properly positioned tissues and organs (cell adhesion and cell migration) Holtfreter: Selective reaggregation of cells from amphibian neurulae Cells segregate and reestablish proper spatial relationships in reaggregation experiments Cells segregate and reestablish proper spatial relationships in reaggregation experiments Models for cell sorting selective affinity (Holtfreter): positive and negative cell-cell interactions differential adhesion (Steinberg): thermodynamic stability (lowest free energy) Cell Adhesion Molecules (CAMs) Cadherins (calcium-dependent) Immunoglobulin superfamily CAMs (calcium-independent) Cadherins link cell-cell adhesion to the cytoskeleton Classes of cadherins E-cadherin (epithelial cadherin) P-cadherin (placental cadherin) N-cadherin (neural cadherin) EP-cadherin (C cadherin) Protocadherins (lack connection to cytoskeleton via catenins) Types of cell adhesion molecule (CAM) interaction homophilic (homotypic): binding of a CAM on one cell to a CAM of the same type on another cell heterophilic (heterotypic): binding of one type of CAM on one cell to a CAM of a different type on another cell Depletion of EP-cadherin activity disorganizes the Xenopus blastula
control EP-cadherin-depleted antisense oligonucleotides E-cadherin N-cadherin Expression of distinct cadherins in different tissues during neurulation Loss of N-cadherin function in the Xenopus embryo disorganizes the neural tube Left side: N-cadherin dominant negative (lacking the extracellular domain) Experimental alteration of cadherin expression pattern in the Xenopus (frog) embryo interferes with neurulation normal development ectopic N-cadherin mRNA Sorting out in vivo: The fly oocyte is positioned by E-cadherin-mediated adhesion
Normal egg chamber When anterior cells express more E-cadherin N-cadherin is required for proper cone cell patterning in the fly eye Green: N-cadherin "Soap bubble" configuration of cone cells minimizes surface area
Hayashi, T., and Carthew, R. W. (2004) Nature 431: 647-652 Purple: N-cadherin-positive Green: -catenin Two Major Cell States epithelium: organized layer (sheet or tube) of adherent, tightly connected cells mesenchyme: loose association of individual cells, often migrating or preparing to migrate Sea urchin gastrulation Ingression of sea urchin primary mesenchyme cells involves changes in cell affinity PMCs only: (1) Loss of affinity for hyaline layer (2) Decrease in affinity for adjacent vegetal plate cells and for each other (3) Increase in affinity for basal lamina Two Major Cell State Transitions epithelial-mesenchymal transition: separation of single cells from an organized layer of connected cells, often in preparation for migration mesenchymal-epithelial transition: coalescence of individual cells (often postmigration) into an organized connected layer Neural crest cells arise from a localized epithelialmesenchymal transition Formation of the chick heart endocardium from splanchnic lateral plate mesoderm involves both epithelialmesenchymal and mesenchymal -epithelial transitions The mesoderm of the chick embryo arises initially from an epithelial-mesenchymal transition Chick mesoderm undergoes a mesenchymal-epithelial transition to assemble into distinct subdivisions lateral to the neural tube neural crest cells somite Somite formation involves the assembly of a tight epithelium from segments of paraxial mesoderm
somitomere Somites are a transient epithelial state of paraxial mesoderm N-cadherin expression at different stages of paraxial mesoderm development in the chick embryo Somite differentiation is accompanied by epithelialmesenchymal transitions in the sclerotome and dermamyotome An epithelialmesenchymal transition in somatic lateral plate mesoderm creates the precursors to the skeletal elements of the limb ...
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