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

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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

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