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doi: 10.1242/10.1242/dev.00506


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Development 130, 2705-2716 (2003)
Copyright © 2003 The Company of Biologists Limited

Ogon/Secreted Frizzled functions as a negative feedback regulator of Bmp signaling

Taijiro Yabe1, Takashi Shimizu1,2, Osamu Muraoka2, Young-Ki Bae1,2, Tsutomu Hirata1, Hideaki Nojima1, Atsushi Kawakami3, Toshio Hirano1,4 and Masahiko Hibi1,2,*

1 Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
2 Laboratory for Vertebrate Axis Formation, Center for Developmental Biology, RIKEN, Kobe, Hyogo 650-0047, Japan
3 Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
4 Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan

* Author for correspondence (e-mail: hibi{at}cdb.riken.go.jp)

Accepted 20 March 2003

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.

Key words: Zebrafish, Ogon, Sizzled, Bmp, Chordin, Dorsoventral patterning, Feedback inhibitor




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