Publicação
Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior
| Resumo: | 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. |
|---|---|
| Autores principais: | Wircer, Einav |
| Outros Autores: | Blechman, Janna; Borodovsky, Nataliya; Tsoory, Michael; Nunes, Ana Rita; Oliveira, Rui Filipe; Levkowitz, Gil |
| Assunto: | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Ispa-Instituto Universitário |
| Idioma: | inglês |
| Origem: | Repositório do Ispa - Instituto Universitário |
| _version_ | 1866886804757544960 |
|---|---|
| author | Wircer, Einav |
| author2 | Blechman, Janna Borodovsky, Nataliya Tsoory, Michael Nunes, Ana Rita Oliveira, Rui Filipe Levkowitz, Gil |
| author2_role | author author author author author author |
| author_facet | Wircer, Einav Blechman, Janna Borodovsky, Nataliya Tsoory, Michael Nunes, Ana Rita Oliveira, Rui Filipe Levkowitz, Gil |
| author_role | author |
| contributor_name_str_mv | Repositório do ISPA |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Wircer, Einav\"},{\"Person.name\":\"Blechman, Janna\"},{\"Person.name\":\"Borodovsky, Nataliya\"},{\"Person.name\":\"Tsoory, Michael\"},{\"Person.name\":\"Nunes, Ana Rita\"},{\"Person.name\":\"Oliveira, Rui Filipe\"},{\"Person.name\":\"Levkowitz, Gil\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório do ISPA |
| datacite.creators.creator.creatorName.fl_str_mv | Wircer, Einav Blechman, Janna Borodovsky, Nataliya Tsoory, Michael Nunes, Ana Rita Oliveira, Rui Filipe Levkowitz, Gil |
| datacite.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2017-03-06T18:56:25Z |
| datacite.date.embargoed.fl_str_mv | 2017-03-06T18:56:25Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| datacite.titles.title.fl_str_mv | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| dc.contributor.none.fl_str_mv | Repositório do ISPA |
| dc.creator.none.fl_str_mv | Wircer, Einav Blechman, Janna Borodovsky, Nataliya Tsoory, Michael Nunes, Ana Rita Oliveira, Rui Filipe Levkowitz, Gil |
| dc.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2017-03-06T18:56:25Z |
| dc.date.embargoed.fl_str_mv | 2017-03-06T18:56:25Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.12/5307 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | eLife Sciences Publications |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| dc.title.fl_str_mv | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ispa.pt/bitstreams/8e8ccdeb-abbc-4423-8f0a-f21f7fa47421/download |
| id | ispa_491d3262ae673906f904bdcbe7aa2da4 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.12/5307 |
| instacron_str | ispa |
| institution | Ispa-Instituto Universitário |
| instname_str | Ispa-Instituto Universitário |
| language | eng |
| network_acronym_str | ispa |
| network_name_str | Repositório do Ispa - Instituto Universitário |
| oai_identifier_str | oai:repositorio.ispa.pt:10400.12/5307 |
| organization_str_mv | urn:organizationAcronym:ispa |
| person_str_mv | Wircer, Einav Blechman, Janna Borodovsky, Nataliya Tsoory, Michael Nunes, Ana Rita Oliveira, Rui Filipe Levkowitz, Gil |
| publishDate | 2017 |
| publisher.none.fl_str_mv | eLife Sciences Publications |
| reponame_str | Repositório do Ispa - Instituto Universitário |
| repository_id_str | urn:repositoryAcronym:ispa |
| service_str_mv | urn:repositoryAcronym:ispa |
| spelling | engeLife Sciences Publicationspt_PTProper 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.application/pdfpt_PTHomeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behaviorWircer, EinavBlechman, JannaBorodovsky, NataliyaTsoory, MichaelNunes, Ana RitaOliveira, Rui FilipeLevkowitz, GilHostingInstitutionOrganizationalRepositório do ISPAe-mailmailto:repositorio@ispa.ptrepositorio@ispa.ptISSNIsPartOf2050-084XDOIIsPartOf10.7554/eLife.221702017-03-06T18:56:25Z20172017-01-01T00:00:00ZHandlehttp://hdl.handle.net/10400.12/5307http://purl.org/coar/access_right/c_abf2open accessParaventricular nucleusReceptor geneMaternal-behaviorLarval zebrafishRainbow-troutCell lineagesPreoptic areaDanio-rerioSpinal-cordBrain9186046 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2017http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ispa.pt/bitstreams/8e8ccdeb-abbc-4423-8f0a-f21f7fa47421/downloadeLife6125United Kingdom |
| spellingShingle | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior Wircer, Einav Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| status | SINGLETON |
| subject.fl_str_mv | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| title | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| title_full | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| title_fullStr | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| title_full_unstemmed | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| title_short | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| title_sort | Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior |
| topic | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| topic_facet | Paraventricular nucleus Receptor gene Maternal-behavior Larval zebrafish Rainbow-trout Cell lineages Preoptic area Danio-rerio Spinal-cord Brain |
| url | http://hdl.handle.net/10400.12/5307 |
| visible | 1 |