1. 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

2. 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?

3. Tissue Formation: Cell Adhesion  Cell surface: same or different amongst cells?  In vitro Tissue culture of cells from the 3 germ layers- Selective affinity

4. Cell Adhesion: differential adhesion.  There is a hierarchy in cell interactions  Strength of interaction will determine fate of cells. Foty et al. 1996

5. 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.

6. 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.

7. 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.

8. 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!

9. Beginning construction of tissues

10. Talking to your neighbors: Paracrine Signaling  Fibroblast Growth factor (FGF)  Hedgehog  Wnt Family  TGF- 

11. FGF  Important for limb and lens development.  Fgf-8 and lens development  Fgf-4 Dachshund and Limb development; More equals less!

12. FGF and Signal Transduction Pathways  RTK signal pathway important for:  Drosophila eye develop.  Nematode vulvae  Human cancers  Jak-Stat Pathway  Ex. Chondrocyte differentiation.

13. 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.

14. 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.

15. TGF-   Largest family  Important classes: TGF-b, activin family, bone morphogenic proteins (BMPs), Vg1 family of proteins (glial derived neurotrophic factor and Mullerian Inhibitory factor).

16. 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.

17. Staying the way you are!  Positive Feedback in transcription  Maintaining Chromatin density  Autocrine.

18. Extracellular Matrix and Develop. Biol.  Cell adhesion  Cell Migration  Formation of epithelial sheets/tubes.  Fibronectin and Laminin  Integrins and the interaction with ECM.

19. Epithelial-Mesenchymal Transition  Paracrine signal initiates transition  Benefits for development?  Benefits for Adulthood?