Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm

  1. Tessa Grace Montague  Is a corresponding author
  2. Alexander F Schier  Is a corresponding author
  1. Harvard University, United States

Abstract

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.

Article and author information

Author details

  1. Tessa Grace Montague

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    tmontague@g.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5918-6327
  2. Alexander F Schier

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    schier@fas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7645-5325

Funding

National Institutes of Health (GM056211)

  • Alexander F Schier

American Society for Engineering Education (National Defense Science and Engineering Graduate Fellowship)

  • Tessa Grace Montague

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Elizabeth Robertson, University of Oxford, United Kingdom

Ethics

Animal experimentation: All vertebrate animal work was performed at the facilities of Harvard University, Faculty of Arts & Sciences (HU/FAS). The HU/FAS animal care and use program maintains full AAALAC accreditation, is assured with OLAW (A3593-01), and is currently registered with the USDA. This study was approved by the Harvard University/Faculty of Arts & Sciences Standing Committee on the Use of Animals in Research & Teaching under Protocol No. 25-08.

Version history

  1. Received: April 28, 2017
  2. Accepted: October 13, 2017
  3. Accepted Manuscript published: November 15, 2017 (version 1)
  4. Accepted Manuscript updated: November 17, 2017 (version 2)
  5. Version of Record published: December 27, 2017 (version 3)

Copyright

© 2017, Montague & Schier

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tessa Grace Montague
  2. Alexander F Schier
(2017)
Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
eLife 6:e28183.
https://doi.org/10.7554/eLife.28183

Share this article

https://doi.org/10.7554/eLife.28183

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