1. Developmental Biology
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Maternal Gdf3 is an obligatory cofactor in nodal signaling for embryonic axis formation in zebrafish

  1. Brent W Bisgrove
  2. Yi-Chu Su
  3. H Joseph Yost  Is a corresponding author
  1. University of Utah, United States
Research Article
  • Cited 3
  • Views 986
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Cite as: eLife 2017;6:e28534 doi: 10.7554/eLife.28534

Abstract

Zebrafish Gdf3 (Dvr1) is a member of the TGFb superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFb ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in gdf3 mutants, indicating that Gdf3 functions at the same pathway step as Nodal.  Targeting gdf3 and ndr2 RNA to specific lineages indicates that exogenous gdf3 is able to fully rescue mutants only when co-expressed with endogenous Nodal. Together, these findings demonstrate that Gdf3 is an essential cofactor of Nodal signaling during establishment of the embryonic axis.

Article and author information

Author details

  1. Brent W Bisgrove

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yi-Chu Su

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. H Joseph Yost

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    For correspondence
    jyost@genetics.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-2961-5669

Funding

National Institutes of Health (2UM1HL098160)

  • H Joseph Yost

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

Ethics

Animal experimentation: All zebrafish research was conducted in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and was approved by the University of Utah IACUC committee (protocol number 15-06004)

Reviewing Editor

  1. Deborah Yelon, Reviewing Editor, University of California, San Diego, United States

Publication history

  1. Received: May 11, 2017
  2. Accepted: November 10, 2017
  3. Accepted Manuscript published: November 15, 2017 (version 1)
  4. Version of Record published: December 27, 2017 (version 2)

Copyright

© 2017, Bisgrove et al.

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. Further reading

Further reading

    1. Developmental Biology
    Jose L Pelliccia et al.
    Research Article Updated

    Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the zebrafish ortholog, Growth differentiation factor 3 (Gdf3), has not been fully explored. We show that zygotic expression of gdf3 is dispensable for embryonic development, while maternally deposited gdf3 is required for mesendoderm formation and dorsal-ventral patterning. We further show that Gdf3 can affect left-right patterning at multiple stages, including proper development of regional cell morphology in Kupffer’s vesicle and the establishment of southpaw expression in the lateral plate mesoderm. Collectively, our data indicate that gdf3 is critical for robust Nodal signaling at multiple stages in zebrafish embryonic development.

    1. Developmental Biology
    Benjamin Tajer, Mary C Mullins
    Insight

    Experiments by three independent groups on zebrafish have clarified the role of two signaling factors, Nodal and Gdf3, during the early stages of development