| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Early spherical Xenopus laevis embryos are transformed into a streamlined shape through convergence and extension movements, or C/E movements. We isolated a neurotrophin receptor-like transmembrane protein, NRH1 (neurotrophin-receptor homolog 1), and have been analyzing the intracellular signaling pathway induced by this factor. In order to find which domain(s) of this protein is in charge for the active induction of C/E movements, we generated several constructs that lacked functional domains. By injecting these mutants into Xenopus embryos, we revealed that the intracellular helical domain, or the death domain, of NRH1 is essential for the induction of the intracellular signaling pathway leading to the C/E movements. Next we performed a yeast two-hybrid screen using this death domain as a belt, and succeeded in isolating Rho GDP dissociation inhibitor (Rho-GDI) as a direct target of NRH1. Isolation of this gene is in a good agreement with the fact that small GTPases such as Rho, Rac or Cdc42 are involved in the C/E movements. Indeed Rho-GDI turned out to regulate the C/E movements in early embryogenesis by gain・and loss-of-function experiments.
We also successfully isolated orthologues of Xenopus NRH from chicken and mouse embryos. They were certainly expressed in the posterior region from early stages of embryogenesis, as Xenopus NRH was, suggesting that NRH functions as a positive regulator of the morphogenetic movements also in chicken and mice.
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