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Curr Biol. 2007 Mar 20;17(6):545-50. Epub 2007 Mar 1.

Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling.

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  • 1Developmental Neurobiology, National Institute for Medical Research, Mill Hill, London, United Kingdom.


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.

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