| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Gastrulation is the first major morphogenetic process in development that entails coordinated cell movements and, ultimately, three germ layers are formed. During Xenopus gastrulation, cells in an equatorial region of the embryo form the leading edge and involute to the inner region of the embryo. They then migrate to the roof of the blastocoel towards the animal poles. Axial mesoderm cells are first polarized and then intercalated in radial and mediolateral directions to cause dramatic extension of the dorsal marginal zone, which is defined as convergent extension, in order to establish the anterior-posterior axis of the body plan. It is known that the process of convergent extension is regulated by the Wnt signaling pathway. We have found that one of the Rab family GTPases is essential for the Wnt signaling pathway. Rab family GTPases are known to regulate many steps of membrane trafficking, and thus we analyzed the roles of Rab GTPases in Xenopus gastrulation. We found that xRab40, a Xenopus homolog of Rab40, was required for normal gastrulation. xRab40 was localized at the Golgi apparatus and was found to interact with ElonginB/C and Cullin5, components of E3 ubiquitin ligases. Loss-of-function of Xenopus Cullin5, designated xCullin5, phenocopied and synergized with xRab40 knockdown. Furthermore, we found that these are essential for the noncanonical Wnt signaling pathway. These results demonstrate that xRab40 and xCullin5 form a ubiquitin ligase complex on the Golgi apparatus and play essential roles during gastrulation through regulating these membrane proteins.
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