Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression
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van Zon-2015-Cells change.pdf
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Author(s)
Kienle, Simone
Huelsz-Prince, Guizela
Barkoulas, Michalis
van Oudenaarden, Alexander
Van Zon, Jeroen Sebastiaan
Date Issued
May 2015
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Van Zon, Jeroen Sebastiaan, Simone Kienle, Guizela Huelsz-Prince, Michalis Barkoulas, and Alexander van Oudenaarden. “Cells Change Their Sensitivity to an EGF Morphogen Gradient to Control EGF-Induced Gene Expression.” Nature Communications 6 (May 11, 2015): 7053. © 2015 Macmillan Publishers Limited
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Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/ncomms8053
