Studies on mechanisms of morphogen action in shaping the body pattern
| Project/Area Number |
10480206
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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 | Institute of Molecular and Cellular Biosciences, The University of Tokyo |
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Principal Investigator |
TABATA Tetsuya Institute of Molecular and Cellular Biosciences, The University of tokyo, Professor, 分子細胞生物学研究所, 教授 (10183865)
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| Co-Investigator(Kenkyū-buntansha) |
TUNEIZUMI Kazuhide Institute of Molecularand Cellular Biosciences The University of tokyo, Instructor, 分子細胞生物学研究所, 助手 (40280953)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥12,200,000 (Direct Cost: ¥12,200,000)
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| Keywords | Morphogen / Dpp / Tkv / p-Mad / Mtv / Gradient / リン酸化Mad / コンパートメント / パターン形成 / dpp / dad / brinker |
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| Research Abstract |
Morphogens have been defined as secreted molecules that emanate from a discrete source, generate a concentration gradient that elicits concentration-dependent responses in target cells and organize pattern and growth of the developmental field Hedgehog (Hh) and Decapentaplegic (Dpp) direct anteroposterior patterning in the developing Drosophila wing by functioning as short-and long-range morphogens, respectively. We show that the activity of Dpp is graded and is dynamically regulated by Engrailed (En)-and Hh-dependent mechanisms. Dpp binds to the receptor complex and signals by phosphorylating the major signal hansducer Mothers against dpp (Mad), which upon phosphorylation translocates into the nucleus and regulates transcription of target genes. Thus the levels of Dpp signaling activity can be monitored in situ by detecting the phospshorylated form of Mad (p-Mad) using a specific antibody. The distribution of p-Mad revealed an unexpectedly complex pattern of Dpp activity in the developing wing ; the gradient of Dpp activity is asymmetric along the A/P axis. Hh downregulates Dpp activity along the A/P compartment border and En is also involved in generating the asymmetric distribution of the Dpp activity gradient. This pattern of the gradient appears to depend largely on the levels of the major type I receptor of Dpp, thickveins (tkv), i.e. the regulatory target of Hh and En is tkv. We found that tkv transcription levels are negatively regulated by a gene that we named master of thick veins (mtv). Hh and Enact through mtv to control the tkv expression pattern, hence mtv plays an important role in shaping the activity gradient of the Dpp morphogen in the developing wing of Drosophila.
We have also identified a new gene brinker (brk) that represses the Dpp target genes. Since brk is downregulated by dpp, it appears that Dpp activates target gene expression by downregulating brk.
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Report
(3 results)
Research Products
(15 results)
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[Publications] Inoue, H., Imamura, T., Ishidou, Y., Takase, M., Udagawa, Y., Oka, Y., Tsuneizumi, K., Tabata, T., Miyazono, K., Kawabata, M.: "Interplay of signal mediators of decapentaplegic (Dpp) : molecular characterization of mothers against dpp, Medea, and daughters against dpp."Mol Biol Cell. 9. 2145-2156 (1998)
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[Publications] Nakayama, T., Synder, M.A., Grewal, S.S., Tsuneizumi, K., Tabata, T., and Cristian, J.L.: "Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning."Development. 125. 857-867 (1998)
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