title: Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression.
abstract: How cells in developing organisms interpret the quantitative information contained in morphogen gradients is an open question. Here we address this question using a novel integrative approach that combines quantitative measurements of morphogen-induced gene expression at single-mRNA resolution with mathematical modelling of the induction process. We focus on the induction of Notch ligands by the LIN-3/EGF morphogen gradient during vulva induction in Caenorhabditis elegans. We show that LIN-3/EGF-induced Notch ligand expression is highly dynamic, exhibiting an abrupt transition from low to high expression. Similar transitions in Notch ligand expression are observed in two highly divergent wild C. elegans isolates. Mathematical modelling and experiments show that this transition is driven by a dynamic increase in the sensitivity of the induced cells to external LIN-3/EGF. Furthermore, this increase in sensitivity is independent of the presence of LIN-3/EGF. Our integrative approach might be useful to study induction by morphogen gradients in other systems.
authors.affiliation: 1] Departments of Physics and Biology and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Jeroen Sebastiaan
authors.initials: JS
authors.lastname: van Zon
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Kienle
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Guizela
authors.initials: G
authors.lastname: Huelsz-Prince
authors.affiliation: 1] Institut de Biologie de l'Ecole Normale Supérieure, CNRS-Inserm-ENS, 46 rue d'Ulm, 75230 Paris cedex 05, France [2] Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Michalis
authors.initials: M
authors.lastname: Barkoulas
authors.affiliation: 1] Departments of Physics and Biology and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D029742:Caenorhabditis elegans Proteins; D051880:Receptors, Notch; D004815:Epidermal Growth Factor; D066246:ErbB Receptors