{"doi":"10.1101/2023.06.07.544119","title":"<i>otpb</i> functions in a Lef1-dependent transcriptional network required for expression of the stress response inhibitor <i>crhbp</i> in the zebrafish hypothalamus","abstract":"Abstract The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish lef1 , which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is otpb , which encodes a transcription factor with known roles in hypothalamic development. Here we show that otpb expression in the posterior hypothalamus is Lef1-dependent, and that like lef1 , its function is required for the generation of crhbp + neurons in this region. Transgenic reporter analysis of a crhbp conserved noncoding element suggests that otpb participates in a transcriptional regulatory network with other Lef1 targets. Finally, consistent with a role for crhbp in inhibiting the stress response, zebrafish otpb mutants exhibit decreased exploration in a novel tank diving assay. Together our findings suggest a potential evolutionarily-conserved mechanism for the regulation of innate stress response behaviors through Lef1-mediated hypothalamic neurogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":408404,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":809476,"name":"Jennifer J. Cheng","orcid":"0000-0002-0531-4725","position":1,"is_corresponding":false},{"id":791565,"name":"Guangning Wang","orcid":null,"position":2,"is_corresponding":false},{"id":1188084,"name":"Cade Kartchner","orcid":null,"position":3,"is_corresponding":false},{"id":1188085,"name":"Debora Brito de Andrade","orcid":null,"position":4,"is_corresponding":false},{"id":1187660,"name":"Harrison Watters","orcid":"0000-0002-8765-2233","position":5,"is_corresponding":false},{"id":1188086,"name":"Ethan Crispell","orcid":null,"position":6,"is_corresponding":false},{"id":1187661,"name":"Richard I. Dorsky","orcid":"0000-0002-8037-6694","position":7,"is_corresponding":false},{"id":1188083,"name":"Priscilla Figueroa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T01:21:18.414003Z","pmid":"37333084","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}