title: Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior.
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 geneotpabut nototpbaffect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus,otpaandotpbdifferentially 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 generalotpa-/-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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Einav
authors.initials: E
authors.lastname: Wircer
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Janna
authors.initials: J
authors.lastname: Blechman
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Borodovsky
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Tsoory
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.|Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Nunes
authors.affiliation: Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal.|ISPA- Instituto Universitário, Lisboa, Portugal.
authors.forename: Rui F
authors.identifier: 0000-0003-1528-618X
authors.initials: RF
authors.lastname: Oliveira
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gil
authors.identifier: 0000-0002-3896-1881
authors.initials: G
authors.lastname: Levkowitz
mesh_terms: D000818:Animals; D007031:Hypothalamus / Q000196:embryology* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012919:Social Behavior; D013312:Stress, Physiological; D013995:Time; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D018045:Receptors, Oxytocin; D014157:Transcription Factors; D029961:Zebrafish Proteins; C515950:orthopedia protein, zebrafish
keywords: autism; developmental biology; hypothalamus; neurodevelopment disorders; neuropeptides; neuroscience; oxytocin; social behavior; stem cells; zebrafish