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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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|
|Date:||09 October 2012|
|Deposited On:||24 Oct 2012 14:50|
|Last Modified:||27 Nov 2013 22:19|
|Publisher:||Nature Publishing Group|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®|
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