The long-term goal of this research is to expand our understanding of the biological basis of craniofacial morphogensesis and the underlying causes of craniofacial anomalies. The main goal of the proposed studies is to understand the contributions of a newly described cell type in craniofacial development. We have recently reported that well, after the emigration of neural crest cells has finished, and additional population of cells emigrates from the neural tube. In contrast to the neural crest, this population originates in the ventral portion of the hindbrain neural tube, emigrates at the point of attachment of the trigeminal nerve, and migrates into craniofacial structures. This had led us to hypothesize that these ventral neural tube cells contribute to the formation of craniofacial tissues. The proposed studies will investigate the precise origin of these cells, the molecules that guide their migration, and their contributions. Neural tube cells of chick embryos will be labeled with fluorescent dye and replication-deficient retroviruses to follow their migration and determine their fate. Molecules that guide their migration will be investigated by immunocytochemical detection of cell surface and extracelluar matrix molecules and by antisense strategy. The importance of this population of cell in craniofacial morphogenesis will be investigated by microsurgical interventions. Our current understanding of craniofacial morphogenesis and malformations is based on the belief that the neural crest is the sole neural tube-derived population that migrates into craniofacial structures. The present study will reveal the contributions of a second neural tube-derived population. Results of this study likely will alter our interpretations of mechanisms of normal development, and of the underlying causes of craniofacial anomalies, which make up about 25 percent of all malformations.
