ZFIN ID: ZDB-PUB-060315-3
Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein
Muraoka, O., Shimizu, T., Yabe, T., Nojima, H., Bae, Y.K., Hashimoto, H., and Hibi, M.
Date: 2006
Source: Nature cell biology   8(4): 329-340 (Journal)
Registered Authors: Bae, Young Ki, Hashimoto, Hisashi, Hibi, Masahiko, Muraoka, Osamu, Nojima, Hideaki, Shimizu, Takashi, Yabe, Taijirou
Keywords: none
MeSH Terms:
  • Animals
  • Body Patterning/physiology*
  • Bone Morphogenetic Proteins/antagonists & inhibitors
  • Bone Morphogenetic Proteins/metabolism
  • Cell Polarity*
  • Cysteine/chemistry
  • Cysteine/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Glycoproteins/antagonists & inhibitors
  • Glycoproteins/metabolism*
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Metalloproteases/antagonists & inhibitors
  • Metalloproteases/metabolism
  • Morphogenesis/genetics
  • Oligonucleotides/pharmacology
  • Phenotype
  • Tolloid-Like Metalloproteinases
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 16518392 Full text @ Nat. Cell Biol.
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.