Segmentation of the vertebrate body is first established during embryogenesis by the periodic formation of pairs of somites — for example, every 120 minutes in mouse, 90 minutes in chicken and 30 minutes in zebrafish — added sequentially from a tissue precursor called the presomitic mesoderm (PSM).
The 'clock and wavefront model' is a theoretical model of somitogenesis proposed by J. Cooke and E. C. Zeeman in which they postulated the existence of an oscillator that sets the pace of somite formation and of a front of maturation of the PSM cells towards a somitic fate.
The identification of the periodic expression pattern of the Hairy1 gene in the PSM provided the first molecular evidence of an oscillator linked to somitogenesis. Genes with such a similar periodic pattern, called cyclic genes, were subsequently identified in other species, suggesting that the clock is conserved among vertebrates.
The position of the wavefront or determination front in the PSM corresponds to specific thresholds of FGF (fibroblast growth factor) and Wnt molecules that are distributed in gradients along the PSM.
PSM cells passing the wavefront become competent to respond to the periodic signal of the clock and are characterized by a bistable state, allowing the simultaneous segmental determination of a cohort of cells in response to the clock.
Retinoic acid is involved in the control of the bilateral symmetry of somite formation by preventing the PSM from responding to the left–right asymmetry machinery.
Whereas the zebrafish oscillator seems to be simpler, the amniote oscillator involves a large network of cyclic genes belonging to three signalling pathways (Notch, Wnt and FGF) and is composed of recurring motifs of negative feedback loops.
The Notch pathway is proposed to synchronize the oscillations between neighbouring PSM cellular oscillators.
The nature and the composition of the segmentation clock pacemaker still remain unidentified.
The body axis of vertebrates is composed of a serial repetition of similar anatomical modules that are called segments or metameres. This particular mode of organization is especially conspicuous at the level of the periodic arrangement of vertebrae in the spine. The segmental pattern is established during embryogenesis when the somites — the embryonic segments of vertebrates — are rhythmically produced from the paraxial mesoderm. This process involves the segmentation clock, which is a travelling oscillator that interacts with a maturation wave called the wavefront to produce the periodic series of somites. Here, we review our current understanding of the segmentation process in vertebrates.
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The authors thank A. Aulehla and to E. Ozbudak for critical reading of the manuscript. Work in the Pourquié laboratory is supported by NIH grant R02HD043,158 to O.P. and by Stowers Institute for Medical Research. O.P. is a Howard Hughes Medical Institute Investigator.
The authors declare no competing financial interests.
Embryonic segments (epithelial blocks of tissue surrounding a cavity called somitocoele) giving rise to the sclerotome (precursors of the axial skeleton) and dermomyotome (precursors of the dermis of the back and skeletal muscles).
- Presomitic mesoderm
A mesoderm-derived mesenchymal tissue lying on both sides of the neural tube that gives rise to the somites.
- Paraxial mesoderm
A mesodermal tissue comprising the head mesoderm and the somitic mesoderm.
- Otic vesicle
One of the paired sacs of invaginated ectoderm that develops into the inner ear.
Group of tetrapod vertebrates including mammals, reptiles and birds, the embryo of which is protected by a membrane called the amnion, in particular from dehydration.
Tissue precursor of the three germ layers during gastrulation.
A segmented organization of the body plan along the anterior–posterior axis.
Synthetic molecules of antisense oligonucleotides used for gene expression knock-down.
Tissue consisting of loosely packed cells.
- Basal lamina
A layer of extracellular matrix that underlies the epithelium and is secreted by the epithelial cells.
- Suprathreshold stimulation
Stimulation of sufficient strength to produce a perceptible effect; in the current context a catastrophe leading to somite determination.
Hypothetical last common ancestor of all bilaterians.
Members of the animal kingdom that have bilateral symmetry — the property of having two similar sides, with definite upper and lower surfaces, and anterior and posterior ends.
- Ultradian oscillator
Oscillator with a period of less than 24 hours.
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Dequéant, ML., Pourquié, O. Segmental patterning of the vertebrate embryonic axis. Nat Rev Genet 9, 370–382 (2008). https://doi.org/10.1038/nrg2320
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Nature Ecology & Evolution (2019)
Journal of Statistical Physics (2019)