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Intercellular coupling amplifies fate segregation during Caenorhabditis elegans vulval development

Giurumescu, Claudiu A. and Sternberg, Paul W. and Asthagiri, Anand R. (2006) Intercellular coupling amplifies fate segregation during Caenorhabditis elegans vulval development. Proceedings of the National Academy of Sciences of the United States of America, 103 (5). pp. 1331-1336. ISSN 0027-8424. PMCID PMC1360524.

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During vulval development in Caenorhabditis elegans, six precursor cells acquire a spatial pattern of distinct cell fates. This process is guided by a gradient in the soluble factor, LIN-3, and by direct interactions between neighboring cells mediated by the Notch-like receptor, LIN-12. Genetic evidence has revealed that these two extracellular signals are coupled: lateral cell-cell interactions inhibit LIN-3-mediated signaling, whereas LIN-3 regulates the extent of lateral signaling. To elucidate the quantitative implications of this coupled network topology for cell patterning during vulval development, we developed a mathematical model of LIN-3/LIN12-mediated signaling in the vulval precursor cell array. Our analysis reveals that coupling LIN-3 and LIN-12 amplifies cellular perception of the LIN-3 gradient and polarizes lateral signaling, both of which enhance fate segregation beyond that achievable by an uncoupled system.

Item Type:Article
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URLURL TypeDescription CentralArticle
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2006 by The National Academy of Sciences of the USA. Published online before print January 23, 2006, 10.1073/pnas.0506476103. Edited by Scott W. Emmons, Albert Einstein College of Medicine, Bronx, NY, and accepted by the Editorial Board December 19, 2005 (received for review July 28, 2005). This paper was submitted directly (Track II) to the PNAS office. S.W.E. is a guest editor invited by the Editorial Board. This work was supported by Institute for Collaborative Biotechnologies Grant DAAD 19-03-D-0004 from the U.S. Army Research Office (to A.R.A.) and a start-up grant from the California Institute of Technology (to A.R.A.). P.W.S. is an investigator with the Howard Hughes Medical Institute.
Funding AgencyGrant Number
Army Research Office (ARO)DAAD 19-03-D-0004
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:multicellular patterning; signal transduction; mitogen-activated protein kinase; gradient amplification; mathematical model
Issue or Number:5
PubMed Central ID:PMC1360524
Record Number:CaltechAUTHORS:GIUpnas06
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3042
Deposited By: Tony Diaz
Deposited On:28 Jul 2006
Last Modified:02 Oct 2019 22:59

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