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Cell-Cell Communication Modes of Cellular Adhesion Movement of Cells/Tissues We’re here, now what? Cell Signaling and differentiation Contacting outside help: Role of Extracellular matrix Epithelial-Mesenchymal Transitions Cell-Cell Communication and Dev. Bio. What makes up a tissue? Location, location, location! What starts organogenesis? More importantly, what determines that it is time to start organogenesis? What determines if a cell continues to grow once an organ begins to form? Which way is what? How do we obtain polarity in the embryo? Tissue Formation: Cell Adhesion Cell surface: same or different amongst cells? In vitro Tissue culture of cells from the 3 germ layersSelective affinity Cell Adhesion: differential adhesion. There is a hierarchy in cell interactions Strength of interaction will determine fate of cells. Foty et al. 1996 Cadherins: Brings cells together! Calcium-dependent adherin molecule. Cadherin-catenin: Classical Adherens junctions. Forms a link with cytoskeleton. Different forms found in different tissues E, P, N, or R-cadherins Migrating cells use protocadherins. Timing and strength of Cadherin Interaction Amount of cadherin on a cell. Cadherin type. Mesenchymal cells of Chick leg: N-cadherin upregulated before condensation. Attachment of Embryo to uterine wall: P-cadherin located in trophoblast cells, not inner mass. Getting away: Cell Motility Polarization occurs, cytoskeleton reorganization. Protrusion of leading edge: Filopodia and Lamellipodia. Adhesion to Extracellular matrix (ECM). Formation of focal adhesions. Release of focal adhesions in trailing edge of cell. Beginning construction of tissues Induction (first identified by Christian Pander). Inducer vs. responder. Inducer: Usually Paracrine factor Responder: cell that changes behavior in response to inducer Initial induction may make cell competent for a second inducer: lens formation. Reciprocal Induction: Returning the favor! Beginning construction of tissues Talking to your neighbors: Paracrine Signaling Fibroblast Growth factor (FGF) Hedgehog Wnt Family TGF-b FGF Important for limb and lens development. Fgf-8 and lens development Fgf-4 Dachshund and Limb development; More equals less! FGF and Signal Transduction Pathways RTK signal pathway important for: Drosophila eye develop. Nematode vulvae Human cancers Jak-Stat Pathway Ex. Chondrocyte differentiation. Hedgehog: Got Cholesterol? 2/3 of protein secreted, cholesterol needed. Limb devel., neural differentiation, and facial morphogenesis. Yes, there is a gene called Sonic Hedgehog. Wnt family: From fly to mammals! Induces dorsal cell of somites to become muscle and specification of the midbrain cells. Similar to Hedgehog..activation of system often accomplished by inhibiting an inhibitor. TGF-b Largest family Important classes: TGF-b, activin family, bone morphogenic proteins (BMPs),Vg1 family of proteins (glial derived neurotrophic factor and Mullerian Inhibitory factor). Talking to Neighbors: Juxtacrine Signaling Eph and ephrin- Signal for attraction or repulsion of cells Notch Proteins- Kidney, pancreas, and heart development. Important receptors for nervous system. Staying the way you are! Positive Feedback in transcription Maintaining Chromatin density Autocrine. Extracellular Matrix and Develop. Biol. Cell adhesion Cell Migration Formation of epithelial sheets/tubes. Fibronectin and Laminin Integrins and the interaction with ECM. Epithelial-Mesenchymal Transition Paracrine signal initiates transition Benefits for development? Benefits for Adulthood?