SOX2 regulates acinar cell development in the salivary gland

  1. Elaine Emmerson
  2. Alison May
  3. Sara Nathan
  4. Noel Cruz Pacheco
  5. Carlos O Lizama
  6. Lenka Maliskova
  7. Ann C Zovein
  8. Yin Shen
  9. Marcus O Muench
  10. Sarah M Knox  Is a corresponding author
  1. The University of Edinburgh, United Kingdom
  2. University of California, San Francisco, United States
  3. Blood Systems Research Institute, United States

Abstract

Acinar cells play an essential role in the secretory function of exocrine organs. Despite this requirement, how acinar cells are generated during organogenesis is unclear. Using the acini-ductal network of the developing human and murine salivary gland, we demonstrate an unexpected role for SOX2 and parasympathetic nerves in generating the acinar lineage that has broad implications for epithelial morphogenesis. Despite SOX2 being expressed by progenitors that give rise to both acinar and duct cells, genetic ablation of SOX2 results in a failure to establish acini but not ducts. Furthermore, we show that SOX2 targets acinar specific genes and is essential for the survival of acinar but not ductal cells. Finally, we illustrate an unexpected and novel role for peripheral nerves in the creation of acini throughout development via regulation of SOX2. Thus, SOX2 is a master regulator of the acinar cell lineage essential to the establishment of a functional organ.

Article and author information

Author details

  1. Elaine Emmerson

    The MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5902-3368
  2. Alison May

    Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sara Nathan

    Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Noel Cruz Pacheco

    Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Carlos O Lizama

    Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lenka Maliskova

    Institute of Human Genetics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ann C Zovein

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Yin Shen

    Institute of Human Genetics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Marcus O Muench

    Blood Systems Research Institute, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8946-6605
  10. Sarah M Knox

    Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States
    For correspondence
    sarah.knox@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7567-083X

Funding

National Institute of Dental and Craniofacial Research (R01DE024188)

  • Elaine Emmerson
  • Alison May
  • Sara Nathan
  • Noel Cruz Pacheco
  • Sarah M Knox

California Institute for Regenerative Medicine

  • Elaine Emmerson

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#AN107810and AN111238) of the University of California San Francisco.

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: March 8, 2017
  2. Accepted: June 13, 2017
  3. Accepted Manuscript published: June 17, 2017 (version 1)
  4. Version of Record published: July 5, 2017 (version 2)

Copyright

© 2017, Emmerson 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. Elaine Emmerson
  2. Alison May
  3. Sara Nathan
  4. Noel Cruz Pacheco
  5. Carlos O Lizama
  6. Lenka Maliskova
  7. Ann C Zovein
  8. Yin Shen
  9. Marcus O Muench
  10. Sarah M Knox
(2017)
SOX2 regulates acinar cell development in the salivary gland
eLife 6:e26620.
https://doi.org/10.7554/eLife.26620

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