Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior

  1. Einav Wircer
  2. Janna Blechman
  3. Nataliya Borodovsky
  4. Michael Tsoory
  5. Ana Rita Nunes
  6. Rui F Oliveira
  7. Gil Levkowitz  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Instituto Gulbenkian de Ciência, Portugal

Abstract

Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH). Single-cell analysis revealed that these neurons project mostly to the hindbrain and spinal cord. Ablation of this neuronal subset specifically reduced adult social preference without affecting stress behavior, thereby uncoupling the contribution of a specific OXT cluster to social behavior from the general otpa-/- deficits. Our findings reveal a new role for Otp in controlling developmental neuropeptide balance in a discrete OXT circuit whose disrupted development affects social behavior.

Article and author information

Author details

  1. Einav Wircer

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Janna Blechman

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Nataliya Borodovsky

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Tsoory

    Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Ana Rita Nunes

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Rui F Oliveira

    Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1528-618X
  7. Gil Levkowitz

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    gil.levkowitz@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3896-1881

Funding

Israel Science Foundation (1511/16)

  • Einav Wircer
  • Janna Blechman
  • Gil Levkowitz

Israel Science Foundation (957/12)

  • Einav Wircer
  • Janna Blechman
  • Nataliya Borodovsky
  • Gil Levkowitz

Israel Science Foundation (2137/16)

  • Janna Blechman
  • Gil Levkowitz

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

Reviewing Editor

  1. Joel K Elmquist, University of Texas Southwestern Medical Center, United States

Ethics

Animal experimentation: All procedures were approved by the Weizmann Institute's Institutional Animal Care and Use Committee protocol (27220516-3)

Version history

  1. Received: October 7, 2016
  2. Accepted: January 16, 2017
  3. Accepted Manuscript published: January 17, 2017 (version 1)
  4. Version of Record published: February 6, 2017 (version 2)

Copyright

© 2017, Wircer 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. Einav Wircer
  2. Janna Blechman
  3. Nataliya Borodovsky
  4. Michael Tsoory
  5. Ana Rita Nunes
  6. Rui F Oliveira
  7. Gil Levkowitz
(2017)
Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior
eLife 6:e22170.
https://doi.org/10.7554/eLife.22170

Share this article

https://doi.org/10.7554/eLife.22170

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