Regulatory factors working in the downstream pathway of the neural inducer Chordin

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n a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by the neural inducer Chordin and suppressed by BMP-4 in a primary response fashion : Zic-related-l (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor.Expression of the two genes are first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin(Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast Sox-2 alone is not sufficient to cause neural differentiation but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.We are also characterizing several other neural-specific molecules induced by chordin, some of which have neuralizing or patterning activities on early ectoderm. I thus elucidated the roles of these molecules including Zic and Sox in the light of early neural patterning. In addition, I have isolated a new transcription factor working in the downstream of Chordin, namely SOX-D.