Projects per year
Abstract
All vertebrates share a segmented body axis. Segments form from the rostral end of the presomitic mesoderm (PSM) with a periodicity that is regulated by the segmentation clock. The segmentation clock is a molecular oscillator that exhibits dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanism by which NICD stability is regulated in this context is unclear. We identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations and an increase in somite size.
Original language | English |
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Article number | e46436 |
Pages (from-to) | 1-22 |
Number of pages | 22 |
Journal | EMBO Reports |
Volume | 20 |
Issue number | 7 |
Early online date | 17 Apr 2019 |
DOIs | |
Publication status | Published - 1 Jul 2019 |
Keywords
- FBXW7
- Notch
- cell cycle
- phosphorylation
- somitogenesis
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
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Dive into the research topics of 'CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock'. Together they form a unique fingerprint.Projects
- 2 Finished
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Fine-Scale Regulation of Notch Signalling Dynamics : In the Context of the Vertebrate Segmentation Clock
Dale, K. (Investigator)
1/08/19 → 31/03/24
Project: Research
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Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research
Profiles
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Dale, Kim
- Molecular Cell and Developmental Biology - Professor of Developmental Molecular Biology
Person: Academic