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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Main Authors:	Wang, Yin, Wang, Xi, Wohland, Thorsten, Sampath, Karuna
Format:	Online
Language:	English
Published:	eLife Sciences Publications, Ltd 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887204/

id	pubmed-4887204
recordtype	oai_dc
spelling	pubmed-48872042016-06-02 Extracellular interactions and ligand degradation shape the nodal morphogen gradient Wang, Yin Wang, Xi Wohland, Thorsten Sampath, Karuna 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. 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Yin Wang, Xi Wohland, Thorsten Sampath, Karuna
spellingShingle	Wang, Yin Wang, Xi Wohland, Thorsten Sampath, Karuna Extracellular interactions and ligand degradation shape the nodal morphogen gradient
author_facet	Wang, Yin Wang, Xi Wohland, Thorsten Sampath, Karuna
author_sort	Wang, Yin
title	Extracellular interactions and ligand degradation shape the nodal morphogen gradient
title_short	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_sort	extracellular interactions and ligand degradation shape the nodal morphogen gradient
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.
publisher	eLife Sciences Publications, Ltd
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887204/
_version_	1613586667863539712

Extracellular interactions and ligand degradation shape the nodal morphogen gradient

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