| 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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| 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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