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XB-ART-34306
Dev Biol November 15, 2006; 299 (2): 398-410.

Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway.

Alexandrova EM , Thomsen GH .


Abstract
The ubiquitin ligase Smurf1 can target a handful of signaling proteins for ubiquitin-mediated proteasomal destruction or functional modification, including TGF-beta receptors, Smads, transcription factors, RhoA and MEKK2. Smurf1 was initially implicated in BMP pathway regulation in embryonic development, but its potential role in vertebrate embryogenesis has yet to be clarified. Here we demonstrate that inhibition of Smurf1 in Xenopus laevis embryos with an antisense morpholino oligonucleotide or a dominant-negative protein disrupts early development, with the nervous system being the principal target. Smurf1 is enriched on the dorsal side of gastrula stage embryos, and blocking Smurf1 disturbs neural folding and neural, but not mesoderm differentiation, enhances BMP/Smad1 signaling, and elevates phospho-Smad1 levels in the dorsal ectoderm. We conclude that in Xenopus embryos, the BMP pathway is a major physiological target of Smurf1, and we propose that in normal development Smurf1 cooperates with secreted BMP antagonists to limit BMP signaling in dorsal ectoderm. Our data also reveal a novel role for Smurf1 and Smad1 in neural plate morphogenesis.

PubMed ID: 16973150
PMC ID: PMC2577174
Article link: Dev Biol
Grant support: [+]
Genes referenced: actl6a ag1 agr2 bmp4 chrd.1 egr2 en2 frzb gal.2 gata6 msx1 ncam1 nkx2-2 otx2 pax6 rhoa shh smad1 smad6 smurf1 smurf2 sox2 tbxt tgfb1 ventx1.2 wnt8a xepsin
Antibodies: Smad1 Ab8 Smurf1 Ab1
Morpholinos: smurf1 MO1


Article Images: [+] show captions
References:
Baker, 2000, Pubmed, Xenbase [+]


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