Molecular mechanisms of neural induction in vertebrates

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The main purpose of this study is to understand what are the switch factors involved in the initiation of neural development in vertebrates. I have established an efficient neural differentiation system using the neural inducer Chordin and Xenopus animal cap, and used this system to analyze early response genes of neural induction. By using the differential hybridization method, several transcription factors have been isolated in the screen for Chordin downstream genes. Three transcription factors (Zic-r1, Sox2, SoxD) are expressed in the neuroectoderm and regulated by Chordin/BMP signaling. Dominant-negative studies have shown that Sox2 and SoxD are essential for neural differentiation of uncommitted ectoderm. In a similar screen, a neural crest-specific gene was also isolated. This gene, FoxD3, encodes a Winged helix-type transcription factor and expressed in the neural crest-forming region of Xenopus gastrula. Overexpression of Fox3 is sufficient to induce neural crest in the animal cap and inhibition of FoxD3 by dnFoxD3 resulted in suppression of neural crest formation.