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A β-catenin gradient links the clock and wavefront systems in mouse embryo segmentation

Nature Cell Biology volume 10, pages 186–193 (2008)Cite this article

Abstract

Rhythmic production of vertebral precursors, the somites, causes bilateral columns of embryonic segments to form. This process involves a molecular oscillator — the segmentation clock — whose signal is translated into a spatial, periodic pattern by a complex signalling gradient system within the presomitic mesoderm (PSM). In mouse embryos, Wnt signalling has been implicated in both the clock and gradient mechanisms, but how the Wnt pathway can perform these two functions simultaneously remains unclear. Here, we use a yellow fluorescent protein (YFP)-based, real-time imaging system in mouse embryos to demonstrate that clock oscillations are independent of β-catenin protein levels. In contrast, we show that the Wnt-signalling gradient is established through a nuclear β-catenin protein gradient in the posterior PSM. This gradient of nuclear β-catenin defines the size of the oscillatory field and controls key aspects of PSM maturation and segment formation, emphasizing the central role of Wnt signalling in this process.

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Figure 1: Conditional stabilization of β-catenin in mouse PSM disrupts somite formation.
Figure 2: Expansion of posterior PSM identity in β-catenindel(ex3)/+ mutant embryos.
Figure 3: Anterior shift of determination front in β-catenindel(ex3)/+ mutant embryos.
Figure 4: Dynamic expression of Wnt and Notch cyclic genes is maintained in β-catenindel(ex3)/+ mutant PSM.
Figure 5: Real-time imaging of Lfng oscillations in control and β-catenindel(ex3)/+ mutant embryos.

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Acknowledgements

We thank members of the Pourquié laboratory for discussions and comments on the manuscript, S. Esteban for artwork and J. Chatfield for manuscript editing. We thank the Stowers Institute Core Facilities, especially D. Dukes and M. Durnin in the Laboratory Animal Service and S. Beckham in the Histology Facility for their excellent technical assistance. A.A was funded by the Swiss Foundation for medical-biological grants, Swiss National Science Foundation. This research was supported by Stowers Institute for Medical Research. O.P. is a Howard Hughes Medical Institute Investigator.

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Authors and Affiliations

  1. Stowers Institute for Medical Research, Kansas City, MO 64110, USA

    Alexander Aulehla, Winfried Wiegraebe, Matthias B. Wahl & Olivier Pourquié

  2. Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, 19104, PA, USA

    Valerie Baubet

  3. Genetics of Development and Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, MD, USA

    Chuxia Deng

  4. Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Makoto Taketo

  5. Laboratory of Cancer and Developmental Biology, NCI-Frederick, National Institutes of Health, Frederick, 21702, MD, USA

    Mark Lewandoski

  6. Howard Hughes Medical Institute, Kansas City, 64110, MO, USA

    Olivier Pourquié

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Contributions

A.A. designed, performed and analysed the experiments; established the real-time imaging and wrote the manuscript. W.W. developed software to analyse the real-time imaging data. V.B. contributed in the initial phase of this project to the real-time imaging experiments. M.W., C.D., M.T. and M.L. provided genetically modified mice. O.P. supervised the project and wrote the manuscript.

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Correspondence to Olivier Pourquié.

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Aulehla, A., Wiegraebe, W., Baubet, V. et al. A β-catenin gradient links the clock and wavefront systems in mouse embryo segmentation. Nat Cell Biol 10, 186–193 (2008). https://doi.org/10.1038/ncb1679

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