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The dual regulator Sufu integrates Hedgehog and Wnt signals in the early Xenopus embryo

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Author

Summary, in English

Hedgehog (Hh) and Wnt proteins are important signals implicated in several aspects of embryonic development, including the early development of the central nervous system. We found that Xenopus Suppressor-of-fused (XSufu) affects neural induction and patterning by regulating the Hh/Gli and Wnt/beta-catenin pathways. Microinjection of XSufu mRNA induced expansion of the epidermis at the expense of neural plate tissue and caused enlargement of the eyes. An antisense morpholino oligonucleotide against XSufu had the opposite effect. Interestingly, both gain- and loss-of-function experiments resulted in a posterior shift of brain markers, suggesting a biphasic effect of XSufu on anteroposterior patterning. XSufu blocked early Wnt/beta-catenin signaling, as indicated by the suppression of XWnt8-induced secondary axis formation in mRNA-injected embryos, and activation of Wnt target genes in XSufu-MO-injected ectodermal explants. We show that XSufu binds to XG*i1 and X beta-catenin. In Xenopus embryos and mouse embryonic fibroblasts, Gli1 inhibits Wnt signaling under overexpression of beta-catenin, whereas beta-catenin stimulates Hh signaling under overexpression of Glil. Notably, endogenous Sufu is critically involved in this crosstalk The results suggest that XSufu may act as a common regulator of Hh and Wnt signaling and contribute to intertwining the two pathways. (C) 2011 Elsevier Inc. All rights reserved.

Department/s

Publishing year

2011

Language

English

Pages

262-276

Publication/Series

Developmental Biology

Volume

358

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Keywords

  • Suppressor-of-fused
  • Gli
  • beta-Catenin
  • Neural
  • Xenopus

Status

Published

ISBN/ISSN/Other

  • ISSN: 1095-564X