Project/Area Number |
16K08444
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General anatomy (including histology/embryology)
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Research Institution | Hiroshima University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
鈴木 厚 広島大学, 両生類研究センター, 准教授 (20314726)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 神経誘導 / 頭部形成 / BMP / Wnt / 発生・分化 / 神経形成 / 先天異常学・奇形学 |
Outline of Final Research Achievements |
The vertebrate body is organized along the dorsal-ventral (DV) and anterior-posterior (AP) axes by the BMP and Wnt pathways, respectively. We reported that BMP inhibitory zinc finger (Biz)/Zbtb14 promotes dorsalization (neuralization) of the ectoderm by inhibiting BMP signal and posteriorizes the induced neural tissue by activating Wnt signal to coordinate DV and AP patterning.
We found that Bap (Biz associated protein) plays an essential role in the regulation of body axis formation. bap and biz/zbtb14 are co-expressed in the dorsal region of the gastrula. Overexpression of Bap together with Biz/Zbtb14 enhanced the activity of Biz/Zbtb14 to induce posterior neural tissue at the expense of epidermis. Knockdown analysis of Bap showed that Bap is required for the formation of posterior neural tissues and repression of anterior neural development. These results suggest that Bap plays an important role in neural development in cooperation with Biz/Zbtb14 to coordinate DV and AP patterning.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は私達が発見したBiz/zbtb14転写因子のBMP・Wntシグナルに対する作用と神経誘導活性を手掛かりとして全前脳胞症発症機構の解明に挑んでいる。Biz/zbtb14とBiz結合因子は全前脳胞症の原因遺伝子座に位置するが神経形成における働きは不明である。 本研究によって、神経形成におけるBiz/zbtb14とBiz結合因子の機能的な相互作用、およびBMP・Wntシグナルネットワークに対する協調作用が解析されれば全前脳胞症発症機構の解明につながる。また、多くの臓器・器官の形成で重要な働きをするBMP・Wntシグナルの新たな制御機構が解明される可能性があり基礎生物学的にも重要な意義がある。
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