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.
- 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
- MeSH Terms
- Body Patterning/physiology*
- Bone Morphogenetic Proteins/antagonists & inhibitors
- Bone Morphogenetic Proteins/metabolism
- Cell Polarity*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Glycoproteins/antagonists & inhibitors
- Intercellular Signaling Peptides and Proteins/metabolism*
- Metalloproteases/antagonists & inhibitors
- Tolloid-Like Metalloproteinases
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- 16518392 Full text @ Nat. Cell Biol.
Muraoka, O., Shimizu, T., Yabe, T., Nojima, H., Bae, Y.K., Hashimoto, H., and Hibi, M. (2006) Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein. Nature cell biology. 8(4):329-340.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes