A binding site for Gli proteins is essential for <i>HNF-3</i>β floor plate enhancer activity in transgenics and can respond to Shh in vitro

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  • Hiroshi Sasaki
    Osaka University 1 Laboratory of Developmental Biology, Institute for Molecular and Cellular Biology , , 1-3 Yamada-oka, Suita, Osaka 565, Japan
  • Chi-chung Hui
    555 University Avenue, Toronto 2 Program in Developmental Biology and Division of Endocrinology, Research Institute, The Hospital for Sick Children , , Ontario M5G 1X8, Canada
  • Masato Nakafuku
    3 Division of Signal Transduction and Metabolic Regulation in Animal Cells, Graduate School of Biological Sciences, Nara Advanced Institute of Science and Technology, Ikoma, Nara 630-01, Japan
  • Hisato Kondoh
    Osaka University 1 Laboratory of Developmental Biology, Institute for Molecular and Cellular Biology , , 1-3 Yamada-oka, Suita, Osaka 565, Japan

Description

<jats:title>ABSTRACT</jats:title> <jats:p>The floor plate plays important roles in ventral pattern formation and axonal guidance within the neural tube of vertebrate embryos. A critical event for floor plate development is the induction of a winged helix transcription factor, Hepatocyte Nuclear Factor-3β (HNF-3β). The enhancer for floor plate expression of HNF-3β is located 3′ of the transcription unit and consists of multiple elements. HNF-3β induction depends on the notochord-derived signal, Sonic hedgehog (Shh). Genetic analysis in Drosophila has led to the identification of genes involved in the Hh signalling pathway, and cubitus interruptus (ci), encoding a protein with five zinc finger motifs, was placed downstream. In the present work, we test the involvement of Gli proteins, the mouse homologues of Ci, in activation of the floor plate enhancer of HNF-3β. Transgenic analysis shows that a Gli-binding site is required for the activity of the minimal floor plate enhancer of HNF-3β in vivo. Three Gli genes are differentially expressed in the developing neural tube. Gli expression is restricted to the ventral part, while Gli2 and Gli3 are expressed throughout the neural tube and dorsally, respectively. Strong Gli and Gli2, and weak Gli3 expressions transiently overlap with HNF-3β at the time of its induction. Consistent with ventrally localized expression, Gli expression can be up-regulated by Shh in a cell line. Finally, the Gli-binding site acts as a Shh responsive element, and human GLI, but not GLI3, can activate this binding site in tissue culture. Taken together, these findings suggest that Gli, and probably also Gli2, are good candidates for transcriptional activators of the HNF-3β floor plate enhancer, and the binding site for Gli proteins is a key element for response to Shh signalling. These results also support the idea that Gli/Ci are evolutionary conserved transcription factors in the Hedgehog signalling pathway.</jats:p>

Journal

  • Development

    Development 124 (7), 1313-1322, 1997-04-01

    The Company of Biologists

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