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Osteogenic transcription factor Runx2 is a maternal determinant of dorsoventral patterning in zebrafish

Nature Cell Biology volume 10, pages 346352 (2008) | Download Citation

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Abstract

The maternal genome greatly influences vertebrate embryogenesis before activation of zygotic transcription. Dorsoventral patterning is initiated by maternal factors1,2,3, but the molecular pathways involved are incompletely understood. In frogs and fish, localized zygotic domains are induced whereby cells either express dorsal or ventral genes1,2. Wnt/β-catenin signalling promotes expression of the earliest dorsal zygotic genes4. Among key zygotic ventralizing factors are the bone morphogenetic proteins (Bmps)5,6 and the Vent homeodomain family2,7,8,9,10; the latter act as repressors of dorsal organizer gene transcription. Here we show that Runx2, a transcription factor essential for bone formation, is an important maternal determinant of ventral zygotic genes in zebrafish. Depletion of maternal Runx2b type2 strongly dorsalizes embryos, due to loss of the earliest zygotic expression of vox, vent and ved, resulting in expansion of dorsal gene expression. To date, Runx2b is the only known regulator of vox, vent and ved at the onset of zygotic transcription; we show that this regulation is direct. Runx2 transcripts are processed in mature mouse oocytes11 and we show that murine Runx2 type2 can substitute for the zebrafish orthologue in its ventralizing function, suggesting that Runx2 may have an evolutionarily conserved role in axis formation.

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Acknowledgements

We thank Alhad Mahagaonkar and Lisa Pullin for technical assistance. We are grateful to M. Hammerschmidt, M. Hibi, T. Komori, D. Kimelman and M. Mullins for sharing their reagents. We thank M. Hibi for his advice on the manuscript. The work was funded by grants from the Health Research Council of New Zealand and the Foundation for Research, Science and Technology, New Zealand. E.Y.L. was supported by Bright Futures Top Achievers Doctoral Scholarship.

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  1. Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

    • Maria Vega C. Flores
    • , Enid Yi Ni Lam
    • , Kathryn E. Crosier
    •  & Philip S. Crosier

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Contributions

M. V. C. F. designed and performed the experimental work, analysed the data and wrote the manuscript. E. Y. L. performed some experiments and the statistical analysis. K. E. C. and P. S. C. planned the project and reviewed the manuscript.

Corresponding author

Correspondence to Philip S. Crosier.

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DOI

https://doi.org/10.1038/ncb1697