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One-Eyed Pinhead and Spadetail are essential for heart and somite formation

Abstract

Mutant analysis in the zebrafish Danio rerio has demonstrated distinct developmental roles for the T-box transcription factor Spadetail (Spt)1 and the Nodal-receptor cofactor One-Eyed Pinhead (Oep)2 in the formation of mesoderm and endoderm. Here, we show that spt and oep genetically interact and are together essential for the formation of cardiac and somitic mesoderm. These two mesodermal defects are dependent on different effectors of Nodal signalling; cardiac mesoderm formation involves the mix-like transcription factor Bonnie and Clyde (Bon)3, whereas somitogenesis is dependent on a different pathway. Analysis of the somite defect in Zoep;spt embryos has provided insights into the control of somitic mesoderm formation by Spt, which was previously implicated in the regulation of cell adhesion and motility4,5. We show that the failure to form somites in Zoep;spt embryos is independent of this and that Spt must have an additional function. We propose that the major role of Spt in somitogenesis is to promote the differentiation of presomitic mesoderm from tailbud progenitors by antagonizing progenitor-type gene expression and behaviour.

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Figure 1: Zoep;spt double-mutant embryos lack somites and heart.
Figure 2: Bonnie and spt interact in the formation of heart, but not somites.
Figure 3: Zoep and spt interact in a novel pathway in presomitic mesoderm.
Figure 4: Spt and Zoep regulate cardiac and presomitic mesoderm formation.

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Acknowledgements

K.J.P.G. wishes to dedicate this paper to the memory of the late Nigel Holder. We wish to thank S. Wilson and R. Warga for mutant lines; D. Yelon, D. Stainier, A. Rodaway, A. Lekven and D. Grunwald for reagents and probes. We are especially grateful to L. Trinh, Y. Kikuchi and D. Stainier for the gift of cas and bon MOs, and D. Meyer for communicating results prior to publication, and for additional analysis of the Zsur;spt embryos. We thank S. Hauschka, D.Raible, A. Schier, B. Draper, D. Kane, R. Warga, S. Amacher, C. Kimmel, C. Viviano and members of the Kimelman lab for valuable comments and discussions; K. Liu and L. Swaim for maintaining the fish facility. This work was supported by National Science Foundation grant IBN-9722949 to D.K.

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Correspondence to David Kimelman.

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Griffin, K., Kimelman, D. One-Eyed Pinhead and Spadetail are essential for heart and somite formation. Nat Cell Biol 4, 821–825 (2002). https://doi.org/10.1038/ncb862

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