The Role of Neural Crest in Facial Patterning

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DESCRIPTION (provided by applicant): My long-term career objective is to investigate the cellular and molecular bases for normal and abnormal facial development. My research will provide a foundation for generating biologically based therapies to treat facial malformations in humans. To prepare for my career, I have received multidisciplinary training in embryology, anatomy, developmental molecular biology, and craniofacial anomalies. Through this diverse background I have acquired skills for studying complex cellular and molecular mechanisms that pattern the developing face. Future progress in understanding normal and abnormal facial morphogenesis will come from discovering and experimentally manipulating molecular and cellular signals that pattern the skeletal, muscular, nervous, and vascular systems of the head. Therefore, in order to provide a substantial contribution to this area of research, I am focusing my work on the regulation of cell differentiation, which is an essential component of craniofacial development. Disruptions to this process result in a range of human birth defects. For example, premature cell differentiation within the osteogenic front of cranial sutures causes craniosynostoses. Conversely, a delay in differentiation of median edge epithelium leads to clefting of the secondary palate. Thus, the timing of differentiation among multiple populations of embryonic cells is a prerequisite for normal facial patterning. Cellular and molecular mechanisms through which cranial populations of neural crest, ectoderm, and mesoderm learn when to differentiate into discrete facial structures such as bone, epidermis, and muscle are unknown. I hypothesize that in the developing face, neural crest cells regulate their own temporal differentiation as well as that of ectoderm and mesoderm. To test this hypothesis, I will perform a series of neural crest transplants between two avian species that have significantly different maturation rates, which will alter temporal information being conveyed among populations of donor and host cells. Using a variety of morphological, cellular, and molecular approaches, my analyses will determine whether donor neural crest-derived cartilages and bones, as well as host-derived epidermal and muscular structures develop on a timetable of the donor, host, or a combination of both species. This project is significant in using a novel approach to investigate regulation of facial growth and will provide valuable insights on birth defects.