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...

Descripción completa

Detalles Bibliográficos
Autores: Preiß, Hannes, Kögler, Anna C, Mörsdorf, David, Čapek, Daniel, Soh, Gary H., Rogers, Katherine W., Morales-Navarrete, Hernán, Almuedo-Castillo, María, Müller, Patrick
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/305738
Acceso en línea:http://hdl.handle.net/10261/305738
Access Level:acceso abierto
Palabra clave:ddc:570
id ES_199bf2df328b57d5d7bcf4972bf2f21c
oai_identifier_str oai:digital.csic.es:10261/305738
network_acronym_str ES
network_name_str España
repository_id_str
spelling Regulation of Nodal signaling propagation by receptor interactions and positive feedbackPreiß, HannesKögler, Anna CMörsdorf, DavidČapek, DanielSoh, Gary H.Rogers, Katherine W.Morales-Navarrete, HernánAlmuedo-Castillo, MaríaMüller, Patrickddc:570During 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.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 637840 (QUANTPATTERN) and grant agreement No 863952 (ACE-OF-SPACE)). This work was also funded by the Max Planck Society and the International Max Planck Research School “From Molecules to Organisms”.Peer reviewedeLife Sciences PublicationsEuropean CommissionMax Planck SocietyInternational Max Planck Research SchoolsConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/305738reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/637840info:eu-repo/grantAgreement/EC/H2020/863952http://dx.doi.org/10.7554/eLife.66397Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3057382026-05-22T06:33:51Z
dc.title.none.fl_str_mv Regulation of Nodal signaling propagation by receptor interactions and positive feedback
title Regulation of Nodal signaling propagation by receptor interactions and positive feedback
spellingShingle Regulation of Nodal signaling propagation by receptor interactions and positive feedback
Preiß, Hannes
ddc:570
title_short 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_sort Regulation of Nodal signaling propagation by receptor interactions and positive feedback
dc.creator.none.fl_str_mv Preiß, Hannes
Kögler, Anna C
Mörsdorf, David
Čapek, Daniel
Soh, Gary H.
Rogers, Katherine W.
Morales-Navarrete, Hernán
Almuedo-Castillo, María
Müller, Patrick
author Preiß, Hannes
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_role author
author2 Kögler, Anna C
Mörsdorf, David
Čapek, Daniel
Soh, Gary H.
Rogers, Katherine W.
Morales-Navarrete, Hernán
Almuedo-Castillo, María
Müller, Patrick
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Max Planck Society
International Max Planck Research Schools
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv ddc:570
topic ddc:570
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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/305738
url http://hdl.handle.net/10261/305738
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/637840
info:eu-repo/grantAgreement/EC/H2020/863952
http://dx.doi.org/10.7554/eLife.66397
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404056300027904
score 15.811543

Similares en LA Referencia