Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP-2ε in vomeronasal sensory neurons

Abstract

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remain a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing vomeronasal sensory neurons (VSNs), and vomeronasal dependent behaviors can be reprogrammed through the rescue of Tfap2e/AP-2e expression in the Tfap2eNull mice, and partially reprogrammed by inducing ectopic Tfap2e expression in mature apical VSNs. We suggest that the transcription factor Tfap2e can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 and 6.The scRNA-seq data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession number GSE192746 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192746). We also utilized previously published data from (Katreddi et al., 2021), available through GEO series accession number GSE190330 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190330).The data from this CUT&RUN experiment has been deposited into the NCBI's Expression Omnibus and are accessible through GEO series accession number GSE193139 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193139).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Jennifer M Lin

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9197-0816
  2. Tyler A Mitchell

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Megan Rothstein

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alison Pehl

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ed Zandro M Taroc

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Raghu R Katreddi

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Katherine E Parra

    Department of Psychology, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Damian G Zuloaga

    Department of Psychology, University at Albany, State University of New York, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Marcos Simoes-Costa

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1452-7068
  10. Paolo Emanuele Forni

    Department of Biological Sciences, University at Albany, State University of New York, Albany, United States
    For correspondence
    pforni@albany.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6547-3464

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD097331/HD/NICHD)

  • Paolo Emanuele Forni

National Institute on Deafness and Other Communication Disorders (R01-DC017149)

  • Paolo Emanuele Forni

National Institute of Dental and Craniofacial Research (R01DE028576)

  • Marcos Simoes-Costa

National Institute of Mental Health (R15-MH118692)

  • Damian G Zuloaga

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

Reviewing Editor

  1. Stephen Liberles, Harvard Medical School, United States

Ethics

Animal experimentation: All mouse studies were performed according to the approved Institutional Animal Care and Use Committee (IACUC) protocols (#20-002, #19-001) of the University at Albany.

Version history

  1. Preprint posted: January 14, 2022 (view preprint)
  2. Received: January 21, 2022
  3. Accepted: September 15, 2022
  4. Accepted Manuscript published: September 16, 2022 (version 1)
  5. Version of Record published: September 30, 2022 (version 2)

Copyright

© 2022, Lin 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. Jennifer M Lin
  2. Tyler A Mitchell
  3. Megan Rothstein
  4. Alison Pehl
  5. Ed Zandro M Taroc
  6. Raghu R Katreddi
  7. Katherine E Parra
  8. Damian G Zuloaga
  9. Marcos Simoes-Costa
  10. Paolo Emanuele Forni
(2022)
Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP-2ε in vomeronasal sensory neurons
eLife 11:e77259.
https://doi.org/10.7554/eLife.77259

Share this article

https://doi.org/10.7554/eLife.77259

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