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Title: Cell-cycle regulation of NOTCH signaling during C. elegans vulval development.
Authors: Nusser-Stein, Stefanie
Beyer, Antje
Rimann, Ivo
Adamczyk, Magdalene
Piterman, Nir
Hajnal, Alex
Fisher, Jasmin
First Published: 9-Oct-2012
Publisher: EMBO Press
Citation: Molecular Systems Biology, 2012, 8:618
Abstract: C. elegans vulval development is one of the best-characterized systems to study cell fate specification during organogenesis. The detailed knowledge of the signaling pathways determining vulval precursor cell (VPC) fates permitted us to create a computational model based on the antagonistic interactions between the epidermal growth factor receptor (EGFR)/RAS/MAPK and the NOTCH pathways that specify the primary and secondary fates, respectively. A key notion of our model is called bounded asynchrony, which predicts that a limited degree of asynchrony in the progression of the VPCs is necessary to break their equivalence. While searching for a molecular mechanism underlying bounded asynchrony, we discovered that the termination of NOTCH signaling is tightly linked to cell-cycle progression. When single VPCs were arrested in the G1 phase, intracellular NOTCH failed to be degraded, resulting in a mixed primary/secondary cell fate. Moreover, the G1 cyclins CYD-1 and CYE-1 stabilize NOTCH, while the G2 cyclin CYB-3 promotes NOTCH degradation. Our findings reveal a synchronization mechanism that coordinates NOTCH signaling with cell-cycle progression and thus permits the formation of a stable cell fate pattern.
DOI Link: 10.1038/msb.2012.51
eISSN: 1744-4292
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2012 EMBO and Macmillan Publishers Limited. This is an open-access article distributed under the terms of the Creative Commons Attribution- Non Commercial-ShareAlike Licence ( ).
Appears in Collections:Published Articles, Dept. of Computer Science

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