{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:54:58Z","timestamp":1762660498798,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States\u2013Israel Binational Science Foundation (BSF), Jerusalem, Israel","award":["2019262"],"award-info":[{"award-number":["2019262"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with LHX4 mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. Lhx4-knockout (KO) mice fail to develop a normal AP and die shortly after birth. Here, we characterize a zebrafish lhx4-KO model to further investigate the importance of LHX4 in pituitary gland development and regulation. At the embryonic and larval stages, these fish express lower levels of tshb mRNA compared with their wildtype siblings. In adult lhx4-KO fish, the expressions of pituitary hormone-encoding transcripts, including growth hormone (gh), thyroid stimulating hormone (tshb), proopiomelanocortin (pomca) and follicle stimulating hormone (fshb), are reduced, the pomca promoter-driven expression in corticotrophs is dampened and luteinizing hormone (lhb)-producing gonadotrophs are severely depleted. In contrast to Lhx4-KO mice, Lhx4-deficient fish survive to adulthood, but with a reduced body size. Importantly, lhx4-KO males reach sexual maturity and are reproductively competent, whereas the females remain infertile with undeveloped ovaries. These phenotypes, which are reminiscent of those observed in CPHD patients, along with the advantages of the zebrafish for developmental genetics research, make this lhx4-KO fish an ideal vertebrate model to study the outcomes of LHX4 mutation.<\/jats:p>","DOI":"10.3390\/ijms25137332","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T03:52:58Z","timestamp":1720065178000},"page":"7332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combined Pituitary Hormone Deficiency in lhx4-Knockout Zebrafish"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9509-7860","authenticated-orcid":false,"given":"Nicole","family":"Roisman-Geller","sequence":"first","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odelia","family":"Pisanty","sequence":"additional","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Weinberger","sequence":"additional","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6400-894X","authenticated-orcid":false,"given":"Deodatta S.","family":"Gajbhiye","sequence":"additional","affiliation":[{"name":"Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Volcani Center, Rishon Letziyon 7505101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matan","family":"Golan","sequence":"additional","affiliation":[{"name":"Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Volcani Center, Rishon Letziyon 7505101, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-4128","authenticated-orcid":false,"given":"Yoav","family":"Gothilf","sequence":"additional","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel"},{"name":"Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1159\/000216184","article-title":"Regulation of the hypothalamic-pituitary-adrenal axis","volume":"16","author":"Papadimitriou","year":"2009","journal-title":"Neuroimmunomodulation"},{"key":"ref_2","first-page":"1387","article-title":"Hypothalamus-Pituitary-Thyroid Axis","volume":"6","author":"Chiamolera","year":"2016","journal-title":"Compr. 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