Notch signalling and the synchronization of the somite segmentation clock

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Abstract

In vertebrates with mutations in the Notch cell–cell communication pathway, segmentation fails: the boundaries demarcating somites, the segments of the embryonic body axis, are absent or irregular1,2,3,4,5,6,7,8. This phenotype has prompted many investigations, but the role of Notch signalling in somitogenesis remains mysterious1,9,10,11,12. Somite patterning is thought to be governed by a “clock-and-wavefront” mechanism13: a biochemical oscillator (the segmentation clock) operates in the cells of the presomitic mesoderm, the immature tissue from which the somites are sequentially produced, and a wavefront of maturation sweeps back through this tissue, arresting oscillation and initiating somite differentiation14,15. Cells arrested in different phases of their cycle express different genes, defining the spatially periodic pattern of somites and controlling the physical process of segmentation1,16,17,18,19. Notch signalling, one might think, must be necessary for oscillation, or to organize subsequent events that create the somite boundaries. Here we analyse a set of zebrafish mutants and arrive at a different interpretation: the essential function of Notch signalling in somite segmentation is to keep the oscillations of neighbouring presomitic mesoderm cells synchronized.

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Figure 1: Expression of deltaC in normal sibling embryos fixed at about the 10-somite stage.
Figure 2: deltaC expression patterns in embryos cultured in a temperature gradient, to give faster development on the right side than on the left.
Figure 3: Expression of deltaC and papc in mib, bea, des and aei mutants.
Figure 4: deltaC expression at early stages, from bud to 8 somites.
Figure 5: Signalling pathway proposed to keep oscillations in adjacent cells synchronized in the zebrafish.

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Acknowledgements

We would like to thank J. Campos-Ortega and S. Holley for sharing data before publication; E. de Robertis for the papc probe; Q. Xu for advice on time-lapse filming; and H. McNeill for comments. The work was supported by the Imperial Cancer Research Fund and by an EMBO Fellowship to Y.-J.J.

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Correspondence to Julian Lewis.

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