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A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner

Yojiro Yamanaka, Toshiro Mizuno, Yoshiki Sasai, Masashi Kishi, Hiroyuki Takeda, Cheol-Hee Kim, Masahiko Hibi and Toshio Hirano

Genes & Development, 12: 2345-2353, 1998.

Abstract

The formation of Spemann organizer is one of the most important steps in dorsoventral axis determination in vertebrate development. However, it is controversial whether the organizer forms autonomously or it is induced non-cell-autonomously. In this report, we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically. The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation. Furthermore, dharma expressed in the YSL induced the organizer in a non-cell-autonomous manner. These results provided the first identification of a zygotic gene to be implicated in the formation of an organizer-inducing center.

We named this novel gene dharma, because embryos injected with it form eyes and a head but no trunk or tail, resembling a Japanese dharma doll (named for the famous Buddhist priest).

(PubMed) (Abstract in G & D)(Full Text in G & D)(Œ€‹†‰Ϋ‘θ)

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Colaborating with Talbot and his colleagues and Solnica-Krezel and her colleagues, we showed that the zebrafish dharma gene corrsponds to bozozok (boz) locus. Since boz locus is required at the blastula stages for formation of the embryonic shield, the equivalent of the gastrula organizer and expression of multiple organizer-specific genes and boz is essential for specification of dorsoanterior embryonic structures, including notochord, prechordal mesendoderm, floor plate and forebrain, our studies provide genetic evidence for an essential function of a homeodomain protein, Dharma in beta-catenin-mediated induction of the dorsal gastrula organizer and place dharma/boz at the top of a hierarchy of zygotic genes specifying the dorsal midline of a vertebrate embryo.

References

1) Yamanaka, Y., T. Mizuno, Y. Sasai, M. Kishi, H. Takeda, C.-H. Kim, M. Hibi and T. Hirano. A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner. Genes & Development, 12: 2345-2353, 1998.(Abstract)(PubMed) (Full Text in G & D)@(Œ€‹†‰Ϋ‘θ)

2) Fekany, K., Y. Yamanaka, T. Leung, H. I. Sirotkin, J. Topczewski, M. A. Gates, M. Hibi, A. Renucci, D. Stemple, A. Radbill, A. F. Schier, W. Driver, T. Hirano, W. S. Talbot, and L. Solnica-Krezel. The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures. Development, 126:1427-1438, 1999. (Development), (PubMed)

3) Hashimoto, H., M. Itoh, Y. Yamanaka, S. Yamashita, T. Shimizu, L. Solnica-Krezel, M. Hibi, and T. Hirano. Zebrafish Dkk1 Functions in Forebrain Specification and Axial Mesendoderm Formation. Developmental Biology 217, 138-152, 2000.(Abstract)(PubMed)

4) Shimizu, T., Y. Yamanaka, S.-L. Ryu, H. Hashimoto, T. Yabe, T. Hirata, Y.-K. Bae, M. Hibi, and T. Hirano. Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the formation of the dorsal organizer in zebrafish. Mechanisms of Development, 91, 293-303, 2000.(Full Text)(PubMed)

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