Molecular Systems Biology | |
Cell‐cycle regulation of NOTCH signaling during C. elegans vulval development | |
Stefanie Nusser-Stein3  Antje Beyer1  Ivo Rimann3  Magdalene Adamczyk3  Nir Piterman2  Alex Hajnal3  | |
[1] Department of Genetics, University of Cambridge, Cambridge, UK;Department of Computer Science, University of Leicester, Leicester, UK;Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland | |
关键词: Caenorhabditis elegans; cell cycle; modeling; NOTCH; signal transduction; | |
DOI : 10.1038/msb.2012.51 | |
来源: Wiley | |
【 摘 要 】
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. Through an iterative process of computational modeling, prediction, and experimentation, a molecular synchronization mechanism is revealed by which the cell-cycle regulates Notch signaling to allow the formation of a stable cell fate pattern.Abstract
Synopsis
【 授权许可】
CC BY-NC-SA
Copyright © 2012 EMBO and Macmillan Publishers Limited
Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
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