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Nodal patterning without Lefty inhibitory feedback is functional but fragile

Rogers, Katherine W. and Lord, Nathan D. and Gagnon, James A. and Pauli, Andrea and Zimmerman, Steven and Aksel, Deniz C. and Reyon, Deepak and Tsai, Shengdar Q. and Joung, J. Keith and Schier, Alexander F.. (2017) Nodal patterning without Lefty inhibitory feedback is functional but fragile. eLife, 6. 6:e28785.

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Official URL: https://edoc.unibas.ch/73221/

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Abstract

Developmental signaling pathways often activate their own inhibitors. Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of signaling or mitigate signaling fluctuations, but these models are difficult to rigorously test. Here, we determine whether the ability of the mesendoderm inducer Nodal to activate its inhibitor Lefty is required for development. We find that zebrafish; lefty; mutants exhibit excess Nodal signaling and increased specification of mesendoderm, resulting in embryonic lethality. Strikingly, development can be fully restored without feedback: Lethal patterning defects in; lefty; mutants can be rescued by ectopic expression of; lefty; far from its normal expression domain or by spatially and temporally uniform exposure to a Nodal inhibitor drug. While drug-treated mutants are less tolerant of mild perturbations to Nodal signaling levels than wild type embryos, they can develop into healthy adults. These results indicate that patterning without inhibitory feedback is functional but fragile.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell and Developmental Biology (Schier)
UniBasel Contributors:Schier, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2050-084X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Mar 2020 13:49
Deposited On:31 Mar 2020 13:49

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