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Mech Dev. 2007 Aug;124(7-8):501-17. Epub 2007 Jun 15.

Understanding the somitogenesis clock: what's missing?

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  • 1Howard Hughes Medical Institute and Department of Biochemistry, University of Wisconsin - Madison, 433 Babcock Drive, Madison, WI 53706, USA.


The segmentation of vertebrate embryos depends on a complex genetic network that generates highly dynamic gene expression. Many of the elements of the network have been identified, but their interaction and their influence on segmentation remain poorly understood. A few mathematical models have been proposed to explain the dynamics of subsets of the network, but the mechanistic bases remain controversial. This review focuses on outstanding problems with the generation of somitogenesis clock oscillations, and the ways they could regulate segmentation. Proposals that oscillations are generated by a negative feedback loop formed by Lunatic fringe and Notch signaling are weighed against a model based on positive feedback, and the experimental basis for models of simple negative feedback involving Her/Hes genes or Wnt targets is evaluated. Differences are then made explicit between the many 'clock and wavefront' model variants that have been proposed to explain how the clock regulates segmentation. An understanding of the somitogenesis clock will require addressing experimentally the many questions that arise from the study of simple models.

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