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Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm

Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without matern...

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Detalles Bibliográficos
Autores principales: Montague, Tessa G, Schier, Alexander F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745085/
https://www.ncbi.nlm.nih.gov/pubmed/29140251
http://dx.doi.org/10.7554/eLife.28183
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author Montague, Tessa G
Schier, Alexander F
author_facet Montague, Tessa G
Schier, Alexander F
author_sort Montague, Tessa G
collection PubMed
description Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta-related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal.
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spelling pubmed-57450852018-01-04 Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm Montague, Tessa G Schier, Alexander F eLife Developmental Biology and Stem Cells Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta-related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal. eLife Sciences Publications, Ltd 2017-11-15 /pmc/articles/PMC5745085/ /pubmed/29140251 http://dx.doi.org/10.7554/eLife.28183 Text en © 2017, Montague et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Montague, Tessa G
Schier, Alexander F
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title_full Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title_fullStr Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title_full_unstemmed Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title_short Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
title_sort vg1-nodal heterodimers are the endogenous inducers of mesendoderm
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745085/
https://www.ncbi.nlm.nih.gov/pubmed/29140251
http://dx.doi.org/10.7554/eLife.28183
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