Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein
doi: 10.1038/ncb1379
pmid: 16518392
Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein
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.
- Nagoya University Japan
- University of Wisconsin–Madison United States
- University of Wisconsin–Oshkosh United States
- University of Wisconsin System United States
- Tokai National Higher Education and Research System Japan
Embryo, Nonmammalian, Tolloid-Like Metalloproteinases, Oligonucleotides, Cell Polarity, Gene Expression Regulation, Developmental, Zebrafish Proteins, Phenotype, Bone Morphogenetic Proteins, Metalloproteases, Morphogenesis, Animals, Intercellular Signaling Peptides and Proteins, Cysteine, Zebrafish, Body Patterning, Glycoproteins
Embryo, Nonmammalian, Tolloid-Like Metalloproteinases, Oligonucleotides, Cell Polarity, Gene Expression Regulation, Developmental, Zebrafish Proteins, Phenotype, Bone Morphogenetic Proteins, Metalloproteases, Morphogenesis, Animals, Intercellular Signaling Peptides and Proteins, Cysteine, Zebrafish, Body Patterning, Glycoproteins
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