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

  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  Is a corresponding author
  1. University at Albany, State University of New York, United States
  2. Cornell University, United States

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.

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.

Reviewing Editor

  1. Stephen Liberles, Harvard Medical School, United States

Publication history

  1. Received: January 21, 2022
  2. Accepted: September 15, 2022
  3. Accepted Manuscript published: September 16, 2022 (version 1)

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.

Metrics

  • 102
    Page views
  • 62
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Developmental Biology
    Javier Solivan-Rivera, Zinger Yang Loureiro ... Silvia Corvera
    Research Article Updated

    Mechanisms that control ‘beige/brite’ thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3, and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.

    1. Developmental Biology
    Seok Hee Lee, Xiaowei Liu ... Paolo F Rinaudo
    Research Article Updated

    In vitro fertilization (IVF) has resulted in the birth of over 8 million children. Although most IVF-conceived children are healthy, several studies suggest an increased risk of altered growth rate, cardiovascular dysfunction, and glucose intolerance in this population compared to naturally conceived children. However, a clear understanding of how embryonic metabolism is affected by culture condition and how embryos reprogram their metabolism is unknown. Here, we studied oxidative stress and metabolic alteration in blastocysts conceived by natural mating or by IVF and cultured in physiologic (5%) or atmospheric (20%) oxygen. We found that IVF-generated blastocysts manifest increased reactive oxygen species, oxidative damage to DNA/lipid/proteins, and reduction in glutathione. Metabolic analysis revealed IVF-generated blastocysts display decreased mitochondria respiration and increased glycolytic activity suggestive of enhanced Warburg metabolism. These findings were corroborated by altered intracellular and extracellular pH and increased intracellular lactate levels in IVF-generated embryos. Comprehensive proteomic analysis and targeted immunofluorescence showed reduction of lactate dehydrogenase-B and monocarboxylate transporter 1, enzymes involved in lactate metabolism. Importantly, these enzymes remained downregulated in the tissues of adult IVF-conceived mice, suggesting that metabolic alterations in IVF-generated embryos may result in alteration in lactate metabolism. These findings suggest that alterations in lactate metabolism are a likely mechanism involved in genomic reprogramming and could be involved in the developmental origin of health and disease.