SCHILLING, TF; Univ. of California, Irvine: Craniofacial development and evolution in gnathostomes

The skull and jaws were key innovations in vertebrate evolution. Much of this skeleton has a unique embryonic origin from cranial neural crest cells, unlike the more posterior axial and appendicular skeletons which are derived from mesoderm. How does the embryonic origin of a skeletal element, versus the environment in which it differentiates, determine its morphology and function? Our lab is taking a genetic approach to these issues in zebrafish, and comparing the results with embryos of agnathans and other gnathostomes to identify conserved and divergent genetic pathways. AP-2 transcription factors are required for development of the pharyngeal skeleton, and our analyses of AP2-deficient zebrafish has revealed multiple roles for these factors in early neural crest development. Many of the skeletal defects in embryos lacking a functional AP-2 alpha (tfap2a) are due to intrinsic requirements within neural crest cells themselves, and we have identified a novel target of tfap2a called inca (induced in neural crest by AP-2) that regulates neural crest morphogenesis. In contrast, tfap2b (mutated in some forms of Char syndrome in humans) is required for skeletogenesis but is not expressed in neural crest, only in the epidermis. Epidermal grafts from wild-type donors rescue skeletal development in tfap2b-deficient animals, illustrating the important role that the epidermis plays in modulating skeletogenesis. We have recently shown that the formation of distinct joints between apposing skeletal elements in the jaw also depends on signals from the overlying epidermis. All vertebrate embryos show similar patterns of early neural crest migration, suggesting that differences between species result from dramatic differences in later events such as shifts in the localization and interpretation of signals from adjacent epithelia.