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Extracellular interactions and ligand degradation shape the nodal morphogen gradient

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 processi...

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Detalles Bibliográficos
Autores principales: Wang, Yin, Wang, Xi, Wohland, Thorsten, Sampath, Karuna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887204/
https://www.ncbi.nlm.nih.gov/pubmed/27101364
http://dx.doi.org/10.7554/eLife.13879
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author Wang, Yin
Wang, Xi
Wohland, Thorsten
Sampath, Karuna
author_facet Wang, Yin
Wang, Xi
Wohland, Thorsten
Sampath, Karuna
author_sort Wang, Yin
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.13879.001
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spelling pubmed-48872042016-06-02 Extracellular interactions and ligand degradation shape the nodal morphogen gradient Wang, Yin Wang, Xi Wohland, Thorsten Sampath, Karuna eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.13879.001 eLife Sciences Publications, Ltd 2016-04-21 /pmc/articles/PMC4887204/ /pubmed/27101364 http://dx.doi.org/10.7554/eLife.13879 Text en © 2016, Wang et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Wang, Yin
Wang, Xi
Wohland, Thorsten
Sampath, Karuna
Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_full Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_fullStr Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_full_unstemmed Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_short Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_sort extracellular interactions and ligand degradation shape the nodal morphogen gradient
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887204/
https://www.ncbi.nlm.nih.gov/pubmed/27101364
http://dx.doi.org/10.7554/eLife.13879
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AT sampathkaruna extracellularinteractionsandliganddegradationshapethenodalmorphogengradient