This proposal concerns molecular mechanisms leading to the early development of the vertebrate nervous system, including neural crest cells. The neural crest is a population of stem- cell-like cells, which form in vertebrate embryos at the neural plate border and migrate to diverse locations in the body to give rise to diverse cell types, such as the peripheral nervous system. Neural crest forms as a result of inductive interactions of neuroectoderm, epidermal ectoderm and the underlying mesoderm. The proposed experiments aim to connect cytoskeleton reorganization to neural crest specification. The function of several genes that control actomyosin dynamics will be perturbed to understand the regulatory network that is involved in neural crest formation. These experiments will be carried out in Xenopus embryos, which represent a rapid in vivo system for gene function and allow classical cell biological and biochemical experiments. By connecting upstream regulators, such as Wnt signals, to actin- dependent processes during the initial stages of craniofacial development, the proposed experiments will contribute to the understanding of both the basic developmental mechanisms and are relevant to the disease. A large number of human diseases, such as craniosynostosis, Waardenburg and Hirschsprung's syndromes, and cancer, have been associated with neural crest abnormalities. Studying the mechanisms underlying the development of the neural crest cell should provide insights into human diseases associated with stem cell disorders and cancer.
This application concerns inductive signaling mechanisms regulating the formation of the neural tissue and neural crest cells from embryonic ectoderm. The proposed studies will contribute to the knowledge necessary for prevention of congenital syndromes associated with neural crest abnormalities and relevant to metastatic cancers.
