| Project/Area Number |
12480221
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | The University of tokyo |
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Principal Investigator |
TABATA Tetsuya Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (10183865)
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Noriyuki Tokyo Metropolitan Institute for Neuroscience, Senior Research Scientist, 東京都神経科学総合研究所・分子神経生理学研究部門, 主任研究員 (30300940)
TSUNEIZUMI Kazuhide Institute of Molecular and Cellular Biosciences, Instructer, 分子細胞生物学研究所, 助手 (40280953)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥12,100,000 (Direct Cost: ¥12,100,000)
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| Keywords | Drosophila / Morphogen / HSPG / EXT / ttv / Xenopus / Wnt / PKC / 形態形成 / SNP / dpp / mtv / brk / Xvent2 / FLP-FRT / EGF / engrailed / Dpp / brinker |
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| Research Abstract |
The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) function as morphogens and organize wing patterning in Drosophila.Morphogens emanate from discrete sources and generate concentration gradients that elicit concentration-dependent responses in target cells. We identified two novel Drosophila mutants, sister of tout-velu and brother of tout-velu, and one new allele of tout-velu. The predicted products of these genes belong to an EXT family of proteins that have or are closely related to glycosyltransferase activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutations in these genes reduced protein and signaling levels of Hh, Dpp and Wg. Hh accumulated in front of EXT mutant cells, suggesting that Hh requires HSPGs to move efficiently. We propose that HSPGs facilitate the spreading of morphogens that generates concentration gradients.
Morphogens play an important role in vertebrate development as well. We have studied the signaling pathway by which Wnt, a vertebrate homologue of Wg, regulates early embryogenesis of Xenopus. Although protein kinase C (PKC) has been implicated in the Wnt signaling pathway, its molecular role is poorly understood. We identified novel genes encoding PKCd in Xenopus EST databases. Loss-of-function of PKCd revealed it is essential for convergent extension during gastrulation. Then, we examined relationship between PKCd and the Wnt pathway. PKCd is translocated to the plasma membrane in response to Frizzled signaling. In addition, loss-of-function of PKCd inhibited translocation of Dishevelled and activation of c-Jun N-terminal kinase (JNK) by Frizzled. Furthermore, PKCd forms a complex with Dishevelled ; and activation of PKCd by phorbol ester was sufficient for Dishevelled translocation and JNK activation. PKCd plays an essential role in Wnt/JNK pathway by regulating localization and activity of Dishevelled.
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