Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression
| العنوان: | Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression |
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| المؤلفون: | Alexander van Oudenaarden, Guizela Huelsz-Prince, Michalis Barkoulas, Jeroen S. van Zon, Simone Kienle |
| المساهمون: | Hubrecht Institute for Developmental Biology and Stem Cell Research, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Physics, Koch Institute for Integrative Cancer Research at MIT, van Zon, Jeroen Sebastiaan, van Oudenaarden, Alexander |
| المصدر: | Nature Communications Nature Communications, 6. Nature Publishing Group Nature Communications [E], 6, 7053. Nature Publishing Group Nature Publishing Group |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | General Physics and Astronomy, Biology, Bioinformatics, Research Support, General Biochemistry, Genetics and Molecular Biology, Article, N.I.H, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Research Support, N.I.H., Extramural, Epidermal growth factor, RNA interference, Gene expression, Journal Article, Animals, Humans, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Non-U.S. Gov't, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Transition (genetics), Epidermal Growth Factor, Receptors, Notch, Research Support, Non-U.S. Gov't, Extramural, General Chemistry, biology.organism_classification, 3. Good health, Cell biology, ErbB Receptors, Gene Expression Regulation, RNA Interference, 030217 neurology & neurosurgery, hormones, hormone substitutes, and hormone antagonists, Morphogen |
| الوصف: | 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. National Institutes of Health (U.S.) (National Cancer Institute (U.S.). Physical Sciences-Oncology Center U54CA143874) National Institutes of Health (U.S.) (Pioneer Award 8 DP1 CA174420-05) European Research Council (Advanced Grant ERD-AdG 294325-GeneNoiseControl) |
| وصف الملف: | image/pdf; application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ddfef77fcb67fde7aab6dcea3c083f2cTest https://hdl.handle.net/1874/333260Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ddfef77fcb67fde7aab6dcea3c083f2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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