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Pulses of Notch activation synchronise oscillating somite cells and entrain the zebrafish segmentation clock

Soza-Ried, C; Öztürk, E; Ish-Horowicz, D; Lewis, J; (2014) Pulses of Notch activation synchronise oscillating somite cells and entrain the zebrafish segmentation clock. Development , 141 (8) pp. 1780-1788. 10.1242/dev.102111. Green open access

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Abstract

Formation of somites, the rudiments of vertebrate body segments, is an oscillatory process governed by a gene-expression oscillator, the segmentation clock. This operates in each cell of the presomitic mesoderm (PSM), but the individual cells drift out of synchrony when Delta/Notch signalling fails, causing gross anatomical defects. We and others have suggested that this is because synchrony is maintained by pulses of Notch activation, delivered cyclically by each cell to its neighbours, that serve to adjust or reset the phase of the intracellular oscillator. This, however, has never been proved. Here, we provide direct experimental evidence, using zebrafish containing a heat-shock-driven transgene that lets us deliver artificial pulses of expression of the Notch ligand DeltaC. In DeltaC-defective embryos, in which endogenous Notch signalling fails, the artificial pulses restore synchrony, thereby rescuing somite formation. The spacing of segment boundaries produced by repetitive heat-shocking varies according to the time interval between one heat-shock and the next. The induced synchrony is manifest both morphologically and at the level of the oscillations of her1, a core component of the intracellular oscillator. Thus, entrainment of intracellular clocks by periodic activation of the Notch pathway is indeed the mechanism maintaining cell synchrony during somitogenesis.

Type: Article
Title: Pulses of Notch activation synchronise oscillating somite cells and entrain the zebrafish segmentation clock
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.102111
Publisher version: http://dx.doi.org/10.1242/dev.102111
Language: English
Additional information: Copyright © The Authors 2014. Published by The Company of Biologists Ltd.
Keywords: Delta, Notch, Oscillation, Segmentation clock, Somites, Zebrafish, Animals, Animals, Genetically Modified, Biological Clocks, Cell Count, Embryo, Nonmammalian, Heat-Shock Response, Homeodomain Proteins, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Models, Biological, Nerve Tissue Proteins, Receptor, Notch1, Somites, Time Factors, Transgenes, Zebrafish, Zebrafish Proteins
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1474835
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