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Regulation of Nodal signaling propagation by receptor interactions and positive feedback

During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can als...

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Autores principales: Preiß, Hannes, Kögler, Anna C, Mörsdorf, David, Čapek, Daniel, Soh, Gary H, Rogers, Katherine W, Morales-Navarrete, Hernán, Almuedo-Castillo, María, Müller, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612913/
https://www.ncbi.nlm.nih.gov/pubmed/36149406
http://dx.doi.org/10.7554/eLife.66397
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author Preiß, Hannes
Kögler, Anna C
Mörsdorf, David
Čapek, Daniel
Soh, Gary H
Rogers, Katherine W
Morales-Navarrete, Hernán
Almuedo-Castillo, María
Müller, Patrick
author_facet Preiß, Hannes
Kögler, Anna C
Mörsdorf, David
Čapek, Daniel
Soh, Gary H
Rogers, Katherine W
Morales-Navarrete, Hernán
Almuedo-Castillo, María
Müller, Patrick
author_sort Preiß, Hannes
collection PubMed
description During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish. Here, we characterize three Type I (Acvr1) and four Type II (Acvr2) homologs and show that – except for Acvr1c – all receptor-encoding transcripts are maternally deposited and present during zebrafish embryogenesis. We generated mutants and used them together with combinatorial morpholino knockdown and CRISPR F0 knockout (KO) approaches to assess compound loss-of-function phenotypes. We discovered that the Acvr2 homologs function partly redundantly and partially independently of Nodal to pattern the early zebrafish embryo, whereas the Type I receptors Acvr1b-a and Acvr1b-b redundantly act as major mediators of Nodal signaling. By combining quantitative analyses with expression manipulations, we found that feedback-regulated Type I receptors and co-receptors can directly influence the diffusion and distribution of Nodals, providing a mechanism for the spatial restriction of Nodal signaling during germ layer patterning.
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spelling pubmed-96129132022-10-28 Regulation of Nodal signaling propagation by receptor interactions and positive feedback Preiß, Hannes Kögler, Anna C Mörsdorf, David Čapek, Daniel Soh, Gary H Rogers, Katherine W Morales-Navarrete, Hernán Almuedo-Castillo, María Müller, Patrick eLife Developmental Biology During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish. Here, we characterize three Type I (Acvr1) and four Type II (Acvr2) homologs and show that – except for Acvr1c – all receptor-encoding transcripts are maternally deposited and present during zebrafish embryogenesis. We generated mutants and used them together with combinatorial morpholino knockdown and CRISPR F0 knockout (KO) approaches to assess compound loss-of-function phenotypes. We discovered that the Acvr2 homologs function partly redundantly and partially independently of Nodal to pattern the early zebrafish embryo, whereas the Type I receptors Acvr1b-a and Acvr1b-b redundantly act as major mediators of Nodal signaling. By combining quantitative analyses with expression manipulations, we found that feedback-regulated Type I receptors and co-receptors can directly influence the diffusion and distribution of Nodals, providing a mechanism for the spatial restriction of Nodal signaling during germ layer patterning. eLife Sciences Publications, Ltd 2022-09-23 /pmc/articles/PMC9612913/ /pubmed/36149406 http://dx.doi.org/10.7554/eLife.66397 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Developmental Biology
Preiß, Hannes
Kögler, Anna C
Mörsdorf, David
Čapek, Daniel
Soh, Gary H
Rogers, Katherine W
Morales-Navarrete, Hernán
Almuedo-Castillo, María
Müller, Patrick
Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title_full Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title_fullStr Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title_full_unstemmed Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title_short Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title_sort regulation of nodal signaling propagation by receptor interactions and positive feedback
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612913/
https://www.ncbi.nlm.nih.gov/pubmed/36149406
http://dx.doi.org/10.7554/eLife.66397
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