From signalling oscillations to somite formation

Periodic segmentation of vertebrate embryos or somitogenesis is regulated by a dynamic network of signalling pathways. Signalling gradients determine the spacing of the forming segments, while signalling oscillations, collectively termed the segmentation clock, ensure their regular timing. Since the segmentation clock is a paradigm of signalling dynamics at tissue level, its mechanism and function have been the topic of many studies. Recently, researchers have been able to analyse and quantify these signalling dynamics with unprecedented precision, revealing the complexity of interlinked oscillations and tissue-wide dynamics throughout development. Initial studies have shown how the interplay between signalling dynamics and cellular mechanics drive the periodic formation of segments. Looking ahead, new techniques such as in vitro stem cell-based models of (human) embryonic development will enable detailed investigations into the mechanisms of somitogenesis. During vertebrate development the presomitic mesoderm is periodically segmented into blocks of tissue or somites. Left panel: Signalling gradients and signalling oscillations regulate the sequential segmentation. Middle panel: Neighbouring cells are synchronized through a delayed coupling mechanism, which results in kinematic signalling waves travelling through the tissue from the posterior to the anterior. In mice, oscillations in two different signalling pathways change phase-relationship along this tissue: These are out-of-phase in the posterior and become in-phase in the anterior. Right panel: In mammalian embryos, oscillations in Notch, Wnt and FGF signalling are central components of the so-called segmentation clock. Crosstalk between other signalling pathways, cellular oscillators and tissue mechanics ultimately ensures proper somite formation. (RA: retinoic acid, FGF: fibroblast growth factor, Wnt: Wingless/Integrated, TGFβ: transforming growth factor beta, MET: mesenchymal-to-epithelial transition). [Display omitted]