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Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression

Author

Listed:
  • Jeroen Sebastiaan van Zon

    (Massachusetts Institute of Technology
    FOM Institute AMOLF)

  • Simone Kienle

    (FOM Institute AMOLF)

  • Guizela Huelsz-Prince

    (FOM Institute AMOLF)

  • Michalis Barkoulas

    (Institut de Biologie de l’Ecole Normale Supérieure, CNRS-Inserm-ENS
    Imperial College London)

  • Alexander van Oudenaarden

    (Massachusetts Institute of Technology
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht)

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.

Suggested Citation

  • Jeroen Sebastiaan van Zon & Simone Kienle & Guizela Huelsz-Prince & Michalis Barkoulas & Alexander van Oudenaarden, 2015. "Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8053
    DOI: 10.1038/ncomms8053
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