There are numerous examples during embryogenesis of epithelial layers dispersing to form a mesenchyme--the so-called epithelial/mesenchymal transition. The molecular controls of this process are virtually unknown. The separation of neural crest cells from the early neural tube as they initiate their migration is a prominent example of such a transition. Failure of neural crest cells to migrate produce a wide variety of cranial-facial anomalies including cleft lip and cleft palate and trunk defects including spina bifida and peripheral nervous system deficits. Thus understanding the control of initiation of neural crest migration could tell us much about the cause and prevention-of these defects, as well as provide a framework for understanding the mechanisms controlling other epithelial/mesenchymal transitions. My chief aim is to study the epithelial/mesenchymal transition using the neural crest cell as a model system. I propose to: 1) Label individual presumptive neural crest cells with rhodamine dextran and HRP so that we can visualize for the first time neural crest cells in the process of emigrating out of the neural tube in vivo. This will allow us to determine the methods by which individual cells escape an epithelium and to map what portion of the neural epithelium gives rise to the neural crest. 2) To begin an analysis of the molecular mechanisms that control neural crest emigration by experimentally perturbing extracellular matrix adhesions and cell-cell adhesions in organ and tissue culture and by examining a strain of mutant mice in which initiation of migration is defective. These studies should provide us with the first direct evidence for the control of this important and prevalent morphogenetic process.
