Nature Cell Biology
- 8, 329 - 340 (2006)
Published online: 5 March 2006; | doi:10.1038/ncb1379
There is an Erratum (April 2006) associated with this Article.
Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin proteinOsamu Muraoka1, Takashi Shimizu1, Taijiro Yabe1, 3, Hideaki Nojima1, Young-Ki Bae1, Hisashi Hashimoto2 & Masahiko Hibi11
Laboratory for Vertebrate Axis Formation, Center for Developmental Biology, RIKEN, 2–2–3 Minatojima-minamimachi, Chuo-ku Kobe, Hyogo 650–0047, Japan. 2
Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464–8601, Japan. 3
Present address: Department of Genetics, University of Wisconsin–Madison, Madison, WI 53706, USA.
Correspondence should be addressed to Masahiko Hibi hibi@cdb.riken.jp The Bone morphogenetic protein (Bmp) signalling gradient has a major function in the formation of the dorso-ventral axis. The zebrafish ventralized mutant, ogon, encodes Secreted Frizzled (Sizzled). sizzled is ventrally expressed in a Bmp-dependent manner and is required for the suppression of Bmp signalling on the ventral side of zebrafish embryos. However, it remains unclear how Sizzled inhibits Bmp signalling and controls ventro-lateral cell fate. We found that Sizzled stabilizes Chordin, a Bmp antagonist, by binding and inhibiting the Tolloid-family metalloproteinase, Bmp1a, which cleaves and inactivates Chordin. The cysteine-rich domain of Sizzled is required for inhibition of Bmp1a activity. Loss of both Bmp1a and Tolloid-like1 (Tll1; another Tolloid-family metalloproteinase) function leads to a complete suppression and reversal of the ogon mutant phenotype. These results indicate that Sizzled represses the activities of Tolloid-family proteins, thereby creating the Chordin–Bmp activity gradient along the dorso-ventral axis. Here, we describe a previously unrecognized role for a secreted Frizzled-related protein.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
