Please use this identifier to cite or link to this item: https://doi.org/10.7554/eLife.13879
Title: Extracellular interactions and ligand degradation shape the nodal morphogen gradient
Authors: Wang, Y
Wang, X 
Wohland, T 
Sampath, K
Keywords: enhanced green fluorescent protein
morphogen
activin receptor 2
Acvr2b protein, zebrafish
left right determination factor
Nodal signaling protein
protein binding
zebrafish protein
animal experiment
Article
binding affinity
controlled study
diffusion coefficient
embryo
embryo axis
embryo development
fluorescence correlation spectroscopy
human
human cell
immunoblotting
nonhuman
polymerase chain reaction
protein analysis
protein expression
RNA synthesis
simulation
zebra fish
animal
embryology
metabolism
morphogenesis
protein degradation
spectrofluorometry
Activin Receptors, Type II
Animals
Left-Right Determination Factors
Morphogenesis
Nodal Signaling Ligands
Protein Binding
Proteolysis
Spectrometry, Fluorescence
Zebrafish
Zebrafish Proteins
Issue Date: 2016
Citation: Wang, Y, Wang, X, Wohland, T, Sampath, K (2016). Extracellular interactions and ligand degradation shape the nodal morphogen gradient. eLife 5 (42461) : e13879. ScholarBank@NUS Repository. https://doi.org/10.7554/eLife.13879
Abstract: 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. © Wang et al.
Source Title: eLife
URI: https://scholarbank.nus.edu.sg/handle/10635/174016
ISSN: 2050084X
DOI: 10.7554/eLife.13879
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