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

eLife

Nathan D Lord¹  Philip B Abitua¹  Alexander F Schier²  Adam N Carte³ 

[1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States;Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States;Biozentrum, University of Basel, Basel, Switzerland;Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, United States;Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States;Systems, Synthetic, and Quantitative Biology PhD Program, Harvard University, Cambridge, United States;Biozentrum, University of Basel, Basel, Switzerland;

关键词: nodal signaling;    reaction-diffusion;    patterning;    morphogen;    EGF-CFC;    tgf-beta;    Zebrafish;   

DOI  :  10.7554/eLife.54894

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 and relay, 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 activity spreads 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 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 sensitization of responding cells.

【 授权许可】

CC BY