1998 Fiscal Year Final Research Report Summary
Regulatory factors working in the downstream pathway of the neural inducer Chordin
| Project/Area Number |
09680617
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAI Yoshiki Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (20283616)
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| Project Period (FY) |
1997 – 1998
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| Keywords | neural inducer / neural development / differentiation / transcription factors / SOX / Zic / Chordin / FGF |
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| Research Abstract |
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.
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[Publications] Mizuseki, K., Kishi, M., Matsui, M., Nakanishi, S.and Sasai, Y.: "Xenopus Zic-related-1 and Sox-2, two factors inducer by Chordin, have distinct activities in the initiation of neural induction." Development. 125. 579-587 (1998)
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[Publications] Yamanaka, Y., Mizuno, T., Sasai, Y., Kashi, M., Takeda, H., Hibi, M.and Hirano, T.: "A novel zebrafish homeobox gene, dharma, induces the organizer in a non-cell-autonomous manner." Genes and Dev.12. 2345-2353 (1998)
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