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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-65559

Nusser-Stein, Stefanie; Beyer, Antje; Rimann, Ivo; Adamczyk, Magdalene; Piterman, Nir; Hajnal, Alex; Fisher, Jasmin (2012). Cell-cycle regulation of NOTCH signaling during C. elegans vulval development. Molecular Systems Biology, 8:618.

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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.

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:9 October 2012
Deposited On:24 Oct 2012 12:50
Last Modified:05 Jan 2014 13:04
Publisher:Nature Publishing Group
ISSN:1744-4292
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1038/msb.2012.51
PubMed ID:23047528
Citations:Web of Science®. Times Cited: 4
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Scopus®. Citation Count: 4

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