This project, which will begin its tenth year of support from the NSF, addresses one of the critical questions in developmental biology: how do aa relatively small number of embryonic cells give rise to the multitude of cell types that make up the individual? An ideal model system in which this question can be addressed is the neural crest, which appears very early in the development in all vertebrate species. Although the neural crest is only recognizable for a few days during the course of development, it gives rise to a myriad of important structures in the body. Among the hundreds of neural crest derivatives is the entire peripheral nervous system, all of the pigment cells in the skin and the cells that make the dentin in the teeth. How are such an enormous number of diverse cell types made from a seemingly homogeneous population of cells in a normal individual? With previous NSF support, this laboratory devised sophisticated cell sorting techniques for isolating and studying subpopulations of neural crest cells. Furthermore, they can transplant neural crest cells and follow the transplanted cells throughout development. The current studies will specifically examine how individual neuronal cell types arise from the neural crest by examining the development of two identified subpopulations following transplantation. The events that direct apparently homogeneous neural crest cells to become specific neurons will be examined, and the specific control genes that are associated with these events will be identified. These studies are at the interface of cellular and molecular biology, where, for the first time, it is now possible to address one of the most fundamental questions in developmental neuroscience.