title: Intercellular coupling amplifies fate segregation during Caenorhabditis elegans vulval development.
abstract: 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/LIN-12-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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA 91125, USA.
authors.forename: Claudiu A
authors.initials: CA
authors.lastname: Giurumescu
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.forename: Anand R
authors.initials: AR
authors.lastname: Asthagiri
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D008962:Models, Theoretical; D051880:Receptors, Notch; D015398:Signal Transduction; D014844:Vulva / Q000196:embryology* / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor