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

2017Journal article Open access
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dc.contributor.authorWircer, Einav
dc.contributor.authorBlechman, Janna
dc.contributor.authorBorodovsky, Nataliya
dc.contributor.authorTsoory, Michael
dc.contributor.authorNunes, Ana Rita
dc.contributor.authorOliveira, Rui Filipe
dc.contributor.authorLevkowitz, Gil
dc.date.accessioned2017-03-06T18:56:25Z
dc.date.available2017-03-06T18:56:25Z
dc.date.issued2017
dc.description.abstractProper 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.pt_PT
dc.description.sponsorshipIsrael Science Foundationpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationeLife, 6, 1-25. Doi: 10.7554/eLife.22170pt_PT
dc.identifier.doi10.7554/eLife.22170pt_PT
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/10400.12/5307
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publishereLife Sciences Publicationspt_PT
dc.relation1511/16pt_PT
dc.relation957/12pt_PT
dc.relation2137/16pt_PT
dc.relation.publisherversionhttps://elifesciences.org/content/6/e22170pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectParaventricular nucleuspt_PT
dc.subjectReceptor genept_PT
dc.subjectMaternal-behaviorpt_PT
dc.subjectLarval zebrafishpt_PT
dc.subjectRainbow-troutpt_PT
dc.subjectCell lineagespt_PT
dc.subjectPreoptic areapt_PT
dc.subjectDanio-reriopt_PT
dc.subjectSpinal-cordpt_PT
dc.subjectBrainpt_PT
dc.titleHomeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behaviorpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited Kingdompt_PT
oaire.citation.endPage25pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleeLifept_PT
oaire.citation.volume6pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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