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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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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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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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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DOI: https://doi.org/10.1038/ncb1679
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