Mechanism of HNF3beta induction by a dorsal mesoderm inducer Smad2
Project/Area Number |
09680724
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Developmental biology
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Research Institution | Osaka University |
Principal Investigator |
SASAKI Hiroshi Osaka Univ., Inst.for Molec.and Cell.Biol., Assistant Professor, 細胞生体工学センター, 助手 (10211939)
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Project Period (FY) |
1997 – 1998
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Project Status |
Completed (Fiscal Year 1998)
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Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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Keywords | floor plate / organizer / HNF3beta / enhancer / Sonic hedgehog / Gli / オ-ガナイザー / 遺伝子発現制御 / HNF-3β / Smad2 / nodal |
Research Abstract |
Vertebrate development is controlled by a network of cell-to-cell communications with various intercellular signaling molecules.Thus, it is important to reveal the signal transduction mechanisms to understand development.Previously, we identified enhancers of mouse HNF3beta, which encodes a transcriptional factor important for the development of the organizer, notochord and the floor plate of a neural tube.In this project, we have analyzed the regulatory mechanism of HNF3beta expression by the following two signaling molecules : activin-like signal and Sonic hedgehog (Shh) which regulate development of the organizer/notochord and floor plate, respectively.Firstly, we have tested regulation of HNF3beta by activin signal.With co- transfection assay into cell lines, either an activin signal or its downstream intracellular mediator protein Smad2 did not activate the organizer/notochord enhancer of HNF3beta.These results suggest that expression of HNF3beta is not directly regulated by activin signaling, but it may be regulated by indirect manner through induction of other transcription factors.On the other hand, the Shh signal directly activates HNF3beta.The floor plate enhancer of HNF3beta contains a binding site of Gli family transcription factors.This Gli binding site is essential for the enhancer activity, and it is activated by Shh signaling and by Gli 1 in transfected cells.These results suggest that activation of HNF3beta by Shh signaling is mediated by a transcription factor Gli 1.In addition to the role of induction of HNF3beta, Shh is also involved in ventral pattern formation of a neural tube and somites.Since Gli 1 is also expressed in these regions, it is likely that Gli 1 is a general mediator of Shh signaling.Future analysis of Gli 1 may reveal the molecular mechanism underlying the intercellular comunication by Shh.
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Report
(3 results)
Research Products
(11 results)
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[Publications] Filosa, S., Rivera-Perez, J.A., Gomez, A.P., Gansmuller, A., Sasaki, H., Behringer, R.R.and Ang, S.-L.: "goosecoid and HNF-3beta genetically interact to regulate neural tube patterning during mouse embryogenesis." Development. 124. 2843-2854 (1997)
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[Publications] Ding, Q., Motoyama, J., Gasca, S., Mo, R., Sasaki, H., Rossant, J.and Hui, C.-c.: "Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice." Development. 125. 2533-2543 (1998)
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