Ogon/Secreted Frizzled functions as a negative feedback regulator of Bmp signaling.
The zebrafish mutant ogon (also called mercedes and short tail) displays ventralized phenotypes similar to the chordino (dino) mutant, in which the gene for the Bmp antagonist Chordin is mutated. We isolated the gene responsible for ogon by a positional cloning strategy and found that the ogon locus encodes a zebrafish homolog of Secreted Frizzled (Sizzled), which has sequence similarity to a Wnt receptor, Frizzled. Unlike other secreted Frizzled-related proteins (sFrps) and the Wnt inhibitor Dickkopf1, the misexpression of Ogon/Sizzled dorsalized, but did not anteriorize, the embryos, suggesting a role for Ogon/Sizzled in Bmp inhibition. Ogon/Sizzled did not inhibit a Wnt8-dependent transcription in the zebrafish embryo. ogon/sizzled was expressed on the ventral side from the late blastula through the gastrula stages. The ventral ogon/sizzled expression in the gastrula stage was reduced or absent in the swirl/bmp2b mutants but expanded in the chordino mutants. Misexpression of ogon/sizzled did not dorsalize the chordino mutants, suggesting that Ogon/Sizzled required Chordin protein for dorsalization and Bmp inhibition. These data indicate that Ogon/Sizzled functions as a negative regulator of Bmp signaling and reveal a novel role for a sFrp in dorsoventral patterning.
Yabe
Taijiro
T
Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Shimizu
Takashi
T
Muraoka
Osamu
O
Bae
Young-Ki
YK
Hirata
Tsutomu
T
Nojima
Hideaki
H
Kawakami
Atsushi
A
Hirano
Toshio
T
Hibi
Masahiko
M
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D025461:Feedback, Physiological; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051153:Wnt Proteins; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins
D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C501128:dkk1b protein, zebrafish; C491629:frzb2 protein, Xenopus; C491672:szl protein, zebrafish; C094522:wnt8b protein, zebrafish; C054234:chordin