Key Points
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Vertebrate segmentation depends on an oscillator (the segmentation clock) controlling periodic signalling activities of the Notch, WNT and fibroblast growth factor (FGF) pathways, which act on precursors of the somites in the presomitic mesoderm.
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Spacing of the response to the periodic signal of the clock is controlled by a system of travelling posterior gradients of FGF and WNT signalling. This system leads to the successive determination of embryonic segments along the anteroposterior axis.
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Although the pacemaker of the oscillator has not been fully characterized, delayed negative-feedback loops have been shown to be involved in the control of oscillations in mouse and zebrafish embryos.
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Notch signalling is involved in the synchronization of individual cellular oscillators, resulting in coordinated waves travelling along the presomitic mesoderm.
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Segmental determination occurs in the presomitic mesoderm when segmentation genes such as mesoderm posterior 2 (MESP2) are activated in a striped domain in response to the clock signal. This striped domain specifies the future boundaries of the somite.
Abstract
Segmentation of the paraxial mesoderm is a major event of vertebrate development that establishes the metameric patterning of the body axis. This process involves the periodic formation of sequential units, termed somites, from the presomitic mesoderm. Somite formation relies on a molecular oscillator, the segmentation clock, which controls the rhythmic activation of several signalling pathways and leads to the oscillatory expression of a subset of genes in the presomitic mesoderm. The response to the periodic signal of the clock, leading to the establishment of the segmental pre-pattern, is gated by a system of travelling signalling gradients, often referred to as the wavefront. Recent studies have advanced our understanding of the molecular mechanisms involved in the generation of oscillations and how they interact and are coordinated to activate the segmental gene expression programme.
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Acknowledgements
The authors thank members of the Pourquié laboratory and the referees for comments on the manuscript. A.H. is the recipient of a fellowship from the French Ministry of Higher Education and Research. Research in the Pourquié laboratory is funded by grants of the European Research Council (ERC), the French Muscular Dystrophy Association (AFM), the Human Frontier Science Program (HFSP) and the French National Agency for Research (ANR).
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Glossary
- Paraxial mesoderm
-
The mesoderm that flanks the neural tube in the embryo and that gives rise to the skeletal muscles and axial skeleton.
- Marginal zone
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The superficial region of the embryo that contains the precursors of the mesoderm before they ingress during gastrulation.
- Primitive streak
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The region where cells of the epiblast ingress into the embryo to form the mesoderm during gastrulation.
- Presomitic mesoderm
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(PSM). The most posterior unsegmented region of the paraxial mesoderm, where the segmentation-clock oscillations take place.
- Phase of the oscillator
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The position of an oscillator during its cycle, similar to the position of a hand on a watch. After one period, the oscillator returns to its initial phase.
- Determination front
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The level of the presomitic mesoderm where cells first acquire a defined segmental identity.
- Urbilateria
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The common ancestor of bilaterian animals.
- Nodal signalling
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A pathway downstream of the transforming growth factor-β-like growth factor Nodal that helps to control the asymmetrical development of internal organs such as the heart and liver.
- Hypomorphic mutants
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Mutants showing a weaker phenotype than null mutants.
- Synchronization
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Oscillators are synchronized when they have similar phases (that is, they are 'in phase'). Synchronization can change the oscillation period.
- Coupling strength
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The strength of the interaction involved in synchronizing oscillators between cells.
- Travelling waves
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Also known as kinematic waves. Waves without matter transport or transmission of a signal.
- Doppler effect
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The change of wavelength caused by the displacement of the source.
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Hubaud, A., Pourquié, O. Signalling dynamics in vertebrate segmentation. Nat Rev Mol Cell Biol 15, 709–721 (2014). https://doi.org/10.1038/nrm3891
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DOI: https://doi.org/10.1038/nrm3891
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