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Extracellular interactions and ligand degradation shape the nodal morphogen gradient
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Wang, Yin, Wang, Xi, Wohland, Thorsten and Sampath, Karuna (2016) Extracellular interactions and ligand degradation shape the nodal morphogen gradient. eLife, 5 . e13879. doi:10.7554/eLife.13879 ISSN 2050-084X.
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Official URL: http://dx.doi.org/10.7554/eLife.13879
Abstract
t The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy. We examined the diffusion coefficient of Nodal ligands and Lefty inhibitors in live zebrafish embryos by fluorescence correlation spectroscopy. We also investigated the contribution of ligand degradation to the Nodal gradient. We show that ligand clearance via degradation shapes the Nodal gradient and correlates with its signaling range. By computational simulations of gradient formation, we demonstrate that diffusivity, extra-cellular interactions, and selective ligand destruction collectively shape the Nodal morphogen gradient.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Morphogenesis , Ligands, Transcytosis, Cytonemes, Zebra danio | ||||||||
| Journal or Publication Title: | eLife | ||||||||
| Publisher: | eLife Sciences Publications Ltd. | ||||||||
| ISSN: | 2050-084X | ||||||||
| Official Date: | 21 April 2016 | ||||||||
| Dates: |
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| Volume: | 5 | ||||||||
| Article Number: | e13879 | ||||||||
| DOI: | 10.7554/eLife.13879 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 30 June 2016 | ||||||||
| Date of first compliant Open Access: | 30 June 2016 | ||||||||
| Funder: | Warwick Medical School, National University of Singapore. Graduate Scholarship, Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Singapore. Ministry of Education | ||||||||
| Grant number: | grant MOE2012-T2-1-101: R-154-000-543-112 (Singapore. Ministry of Education) | ||||||||
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