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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-9612913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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