The pattern of nodal morphogen signaling is shaped by co-receptor expression

Lord, Nathan D. and Carte, Adam N. and Abitua, Philip B. and Schier, Alexander F.. (2019) The pattern of nodal morphogen signaling is shaped by co-receptor expression.

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Official URL: https://edoc.unibas.ch/85319/

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Embryos must communicate instructions to their constituent cells over long distances. These instructions are often encoded in the concentration of signals called morphogens. In the textbook view, morphogen molecules diffuse from a localized source to form a concentration gradient, and target cells adopt fates by measuring the local morphogen concentration. However, natural patterning systems often incorporate numerous co-factors and extensive signaling feedback, suggesting that embryos require additional mechanisms to generate signaling patterns. Here, we examine the mechanisms of signaling pattern formation for the mesendoderm inducer Nodal during zebrafish embryogenesis. We find that Nodal signaling activity spans a normal range in the absence of signaling feedback, suggesting that diffusion is sufficient for Nodal gradient formation. We further show that the range of endogenous Nodal ligands is set by the EGF-CFC co-receptor Oep: in the absence of Oep, Nodal ligands spread to form a nearly uniform distribution throughout the embryo. In turn, increasing Oep levels sensitizes cells to Nodal ligands. We recapitulate these experimental results with a computational model in which Oep regulates the diffusive spread of Nodal ligands by setting the rate of capture by target cells. This model predicts, and we confirm in vivo, the surprising observation that a failure to replenish Oep during patterning transforms the Nodal signaling gradient into a travelling wave. These results reveal that patterns of Nodal morphogen signaling are shaped by co-receptor-mediated restriction of ligand spread and cell sensitization.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell and Developmental Biology (Schier)
UniBasel Contributors:Schier, Alexander F and Carte, Adam
Item Type:Preprint
Publisher:Cold Spring Harbor Laboratory
Number of Pages:25
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:29 Mar 2022 11:52
Deposited On:29 Nov 2021 08:17

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