David McClay, Biology

Three areas of major focus of our work have been:

1. on contributions of cell adhesion during two important morphogenetic cell rearrangements in embryos. At gastrulation we have observed a series of molecular changes in adherens junctions and focal contacts. Mesoderm cells at ingression lose both of these adhesive structures and invade the blastocoel. Later, endoderm cells rearrange to form the archenteron, and in the process both adherens junctions and focal contacts are altered. We have cloned cadherins, catenins, and integrins to study these rapid morphogenetic changes that involve an epithelial-mesenchymal cell conversion and convergent-extension cell rearrangements. Our studies focus on the sequence of events involved in that switch from an epithelial cell to a mesenchymal cell, and in the sequence through which the primitive gut is formed. Of importance, Brachyury is involved in the morphogenetic switch that permits archenteron invagination.
   
   
2. to study a number of cell signaling events have been associated with cell rearrangements and pattern formation in the sea urchin embryo. The cell-signaling contributions of hedgehog, ß-catenin, and Notch are being studied as they participate in the correct spatial organization and transmit inductive signals that control specific morphogenetic properties. We have learned that ß-catenin is necessary for vegetal specification and Notch is later utilized to subdivide the vegetal territory into mesoderm. Current efforts are examining the mechanism of these signals and other molecular events that contribute to germ layer specification.
   
   
3. on morphogenesis and pattern formation of the neural tube. We dissect neural tubes of mice as they form. Current analysis examines the detailed molecular adhesion transitions that assist in the folding of the neural tube. The normal morphogenesis is being compared to several mutants with a high penetrance of neural tube defects.