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First published online 5 December 2007
doi: 10.1242/dev.012054

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.012054v1 135/2/237    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alvarez-Medina, R. Articles by Martí, E. Search for Related Content PubMed PubMed Citation Articles by Alvarez-Medina, R. Articles by Martí, E.

Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression

¹ Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, C/Josep Samitier 1-5, Barcelona 08028, Spain.
² Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, Okazaki 444-8787 Japan.

^* Author for correspondence (e-mail: emgbmc{at}ibmb.csic.es)

Accepted 24 October 2007

Dorsoventral patterning of the vertebrate nervous system is achieved by the combined activity of morphogenetic signals secreted from dorsal and ventral signalling centres. The Shh/Gli pathway plays a major role in patterning the ventral neural tube; however, the molecular mechanisms that limit target gene responses to specific progenitor domains remain unclear. Here, we show that Wnt1/Wnt3a, by signalling through the canonical β-catenin/Tcf pathway, control expression of dorsal genes and suppression of the ventral programme, and that this role in DV patterning depends on Gli activity. Additionally, we show that Gli3 expression is controlled by Wnt activity. Identification and characterization of highly conserved non-coding DNA regions around the human Gli3 gene revealed the presence of transcriptionally active Tcf-binding sequences. These indicated that dorsal Gli3 expression might be directly regulated by canonical Wnt activity. In turn, Gli3, by acting as a transcriptional repressor, restricted graded Shh/Gli ventral activity to properly pattern the spinal cord.

Key words: Spinal cord, Neural development, Pattern formation, Wnt canonical signalling, β-catenin, Tcf/Lef1 transcription factors, Hedgehog signalling, Gli transcription factors, Gli3 locus, Mouse, Chick

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