Morphogenesis Differentiation – 2 Cell-cell communication Lecture 10
Sorting out and re-aggregation of embryonic amphibian cells Cells from same germ layer aggregate together. They also seem to maintain their relative position with respect to each other. Selective affinity. Ectoderm has positive affinity towards mesodermal cells and a negative affinity towards endodermal cells while mesoderm has positive affinity for cells from both the germ layers. Townes and Holtfreter, 1955
MS Steinberg
Vade Mecum The differential adhesion hypothesis
Hierarchy of cell sorting Cells rearrange themselves into the most thermodynamically stable pattern. Cell types with greater surface cohesivity migrated centrally compared to cells with less surface cohesion. Steinberg, 1996
Cadherins, 1987 Cadherin mediated cell adhesion Injected with antisense RNA to a cadherin Injected with control antisense RNA
Importance of the amount of cadherin for correct morphogenesis Differential adhesion/surface tension may result out of quantitative difference in cadherin numbers or differences in relative affinities of cadherin pairs
Importance of the type of cadherin for correct morphogenesis
Cell migration 1. Polarization of the cell, defines the front and the back; 2. Protrusion of the leading edge – filopodia (long parallel bundles) and lamellipodia (broad sheets); 3. adhesion of the cell to the ECM (integrins and focal adhesion complex); 4. release of the rear-end of the cell
Induction and competence The optic vesicle is able to induce lens formation in the anterior portion of the ectoderm (1) but not in the presumptive trunk and abdomen (2). If the optic vesicle is removed (3), the surface ectoderm forms either an abnormal lens or no lens at all. Most other tissues are not able to substitute for the optic vesicle (4).
Sequence of amphibian lens induction
Schematic diagram of the induction of the mouse lens
Instructive Versus Permissive interactions Development is a result of a series of interactions EpithelialMesenchymal Epithelial mesenchymal interaction
Genetic specificity of induction in amphibians
It is kind of like our UG students
Juxtacrine signaling Paracrine signaling Autocrine signaling
RTK signaling and FGFs EGF, PDGF, SCF etc.
SCF activates MITF mediated transcription
FGF signaling can also be mediated by JAK-STAT pathway Constitutively activated form of FGFR3 -> STAT1 -> p21 --! Proliferation of chondrocytes