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Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior.
Elife. 2017 01 17; 6E

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.

Authors+Show Affiliations

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal.Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal. ISPA- Instituto Universitário, Lisboa, Portugal.Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28094761

Citation

Wircer, Einav, et al. "Homeodomain Protein Otp Affects Developmental Neuropeptide Switching in Oxytocin Neurons Associated With a Long-term Effect On Social Behavior." ELife, vol. 6, 2017.
Wircer E, Blechman J, Borodovsky N, et al. Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior. Elife. 2017;6.
Wircer, E., Blechman, J., Borodovsky, N., Tsoory, M., Nunes, A. R., Oliveira, R. F., & Levkowitz, G. (2017). Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior. ELife, 6. https://doi.org/10.7554/eLife.22170
Wircer E, et al. Homeodomain Protein Otp Affects Developmental Neuropeptide Switching in Oxytocin Neurons Associated With a Long-term Effect On Social Behavior. Elife. 2017 01 17;6 PubMed PMID: 28094761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior. AU - Wircer,Einav, AU - Blechman,Janna, AU - Borodovsky,Nataliya, AU - Tsoory,Michael, AU - Nunes,Ana Rita, AU - Oliveira,Rui F, AU - Levkowitz,Gil, Y1 - 2017/01/17/ PY - 2016/10/07/received PY - 2017/01/16/accepted PY - 2017/1/18/pubmed PY - 2018/2/6/medline PY - 2017/1/18/entrez KW - autism KW - developmental biology KW - hypothalamus KW - neurodevelopment disorders KW - neuropeptides KW - neuroscience KW - oxytocin KW - social behavior KW - stem cells KW - zebrafish JF - eLife JO - Elife VL - 6 N2 - 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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/28094761/Homeodomain_protein_Otp_affects_developmental_neuropeptide_switching_in_oxytocin_neurons_associated_with_a_long_term_effect_on_social_behavior_ L2 - https://doi.org/10.7554/eLife.22170 DB - PRIME DP - Unbound Medicine ER -