Neural Crest Genes in Craniofacial Development

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DESCRIPTION (provided by applicant): The entirety of the craniofacial skeleton arises from the cranial neural crest, a migratory cell type that forms in the central nervous system, migrates extensively and differentiates into the cartilage and bone of the face. The aim of this proposal is to identify and functionally characterize genes expressed in the cranial neural crest in order to better understand the molecular regulation of craniofacial development. My preliminary results have described a gene expression profile of a premigratory neural crest cell and have identified candidate regulatory molecules involved in craniofacial patterning. In the first phase of the award, the function of two of these genes that are strongly expressed in developing cranial neural crest will be analyzed in detail, and a screen will be carried out to identify new genes expressed during neural crest migration. The role of the receptor neuropilin-2 and its ligands in the cranial neural crest will be analyzed using in vivo and vitro approaches in chicken embryos and in mice bearing neuropilin-2 null mutations. Concomitanity, a gene with no known homology that is highly specific to neural crest precursors will be functionally characterized in chick cranial neural crest by gain-and loss of function techniques. Genes expressed during cranial neural crest migration will be identified in a genome-scale array screen. In the second phase of the award, the function of additional genes will be analyzed through traditional approaches (chick overpression and creation of the mouse mutants) in addition to the proposed construction of a neural crest-specific array that can be used to probe gene expression during cranial neural crest development under different conditions. The Scholar Development Phase of this award will be carried out in the lab of Dr. Marianne Bronner-Fraser at Caltech, a leader in the field of neural crest research at one of the most highly regarded research universities in the country. The candidate, Dr. Laura Gammill, has been a postdoctoral scholar in Dr. Bronner-Fraser's lab since 1999. The candidate's effort thus far has been to create a unique macroarray reagent that was used to identify a large collection of genes involved in early neural crest development. The immediate career goal is to develop research expertise in the area of chick and mouse embryology and to practice mentoring skills so as to obtain an academic faculty position. The long-term career goal is to run a laboratory doing basic research in neural crest and craniofacial development.