Abstract
BackgroundRecent discoveries in the field of somitogenesis have confirmed, for the most part, the feasibility of the clock and wavefront model. There are good candidates for both the clock (various genes expressed cyclically in the tail bud of vertebrate embryos have been discovered) and the wavefront (there are at least three different substances, whose expression levels vary along the presomitic mesoderm [PSM], that have important effects on the formation of somites). Nevertheless, the mechanisms through which the wavefront interacts with the clock to arrest the oscillations and induce somite formation have not yet been fully elucidated.Principal FindingsIn this work, we propose a gene regulatory network which is consistent with all known experimental facts in embryonic mice, and whose dynamic behaviour provides a potential explanation for the periodic aggregation of PSM cells into blocks: the first step leading to the formation of somites.SignificanceTo our knowledge, this is the first proposed mechanism that fully explains how a block of PSM cells can stop oscillating simultaneously, and how this process is repeated periodically, via the interaction of the segmentation clock and the determination front.
Highlights
Segmentation of the body axis is a basic characteristic of many animal species ranging from invertebrates to mammals
Based upon extant experimental evidence on mice embryos, we propose a regulatory network involving two genes in the Notch and Fibroblast Growth Factor (FGF)/Wnt signalling pathways and show that its dynamic behaviour is sufficient to explain the rhythmic segmentation of presomitic mesoderm (PSM) cells in this species
It is known that various genes under the Notch and Wnt signalling pathways oscillate in cells located within the tail bud (TB), where high FGF and Wnt levels are found
Summary
Segmentation of the body axis is a basic characteristic of many animal species ranging from invertebrates to mammals. The vertebrate body is organized, along the antero-posterior (AP) axis, in a series of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves, and blood vessels. These units originate from the earlier pattern of the embryonic somites, which are blocks of cells generated in a rhythmic fashion from the mesenchymal presomitic mesoderm (PSM). The clock and wavefront model of Cooke and Zeeman [1] has found the widest acceptance and applicability According to this model, reviewed in [2], the segmental pattern is established in the PSM by a mechanism involving an oscillator (the segmentation clock), which is hypothesized to set the periodicity of the process, and a travelling wavefront of cell change that sweeps anteriorly to posteriorly through the PSM, arresting the oscillation, and inducing (or permitting) somite maturation. The mechanisms through which the wavefront interacts with the clock to arrest the oscillations and induce somite formation have not yet been fully elucidated
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