Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling

Fausto Ulloa, Nobue Itasaki, James Briscoe

Research output: Contribution to journalArticle (Academic Journal)

83 Citations (Scopus)

Abstract

The Hedgehog (Hh) and Wingless (Wnt) families of secreted signaling molecules have key roles in embryonic development and adult tissue homeostasis [1-3]. In the developing neural tube, Wnt and Shh, emanating from dorsal and ventral regions, respectively, have been proposed to govern the proliferation and survival of neural progenitors [4-10]. Surprisingly, Shh is required for the growth and survival of cells in both ventral and dorsal neural tube [11]. Here we demonstrate that inhibition of Shh signaling causes a reduction in Wnt-mediated transcriptional activation. This reduction requires Gli3. Assays in embryos and cell lines indicate that repressor forms of the Hh-regulated transcription factor, Gli3 (Gli3R), which are generated in the absence of Hh signaling, inhibit canonical Wnt signaling. Gli3R acts by antagonizing active forms of the Wnt transcriptional effector, beta-catenin. Consistent with this, Gli3R appears to physically interact with the carboxy-terminal domain of beta-catenin, a region that includes the transactivation domain. These data offer an explanation for the proliferative defects in Shh null embryos and suggest a novel mechanism for crosstalk between the Hh and Wnt pathways.

Original languageEnglish
Pages (from-to)545-550
Number of pages6
JournalCurrent Biology
Volume17
Issue number6
Early online date1 Mar 2007
DOIs
Publication statusPublished - 20 Mar 2007

Keywords

  • Animals
  • Chick Embryo
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Embryonic Development
  • Gene Expression Regulation
  • Hedgehog Proteins
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice
  • Nerve Tissue Proteins
  • Protein Interaction Mapping
  • Signal Transduction
  • Wnt Proteins
  • Wnt3 Protein
  • Xenopus
  • beta Catenin

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