My long term career objective is to conduct independent, clinically relevant basic science research. My research interests are in the molecular mechanisms that underlie development of the craniofacial tissues. Craniofacial abnormalities affect hundreds of thousands of children each year causing physical, emotional and economic hardships for the child and their families. It has been recognized for over 50 years that deficiencies, and excesses, in vitamin A or its biological metabolite, retinoic acid, is associated with severe craniofacial defects. These defects frequently include cleft lip and palate, and malformations of the middle and external ear. Although the precise molecular mechanisms that underlie this process remains poorly understood, these studies are, highly suggestive of a role for a nuclear receptor such as RA and its receptor in craniofacial development. In this proposal, I will study the role of nuclear receptors in one of the earliest events in formation of the craniofacial structures, hindbrain segmentation. We will isolate nuclear receptors expressed during early vertebrate neurogenesis, and describe their temporal and spatial patterns of expression using in situ analysis. We will also investigate the effects of cell interactions on nuclear receptor gene expression using transplantation experiments.