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However, the molecular mechanisms underlying its formation and function have not been clearly elucidated. Various mutations in the human <jats:italic>COUP<\/jats:italic>-<jats:italic>TFII<\/jats:italic> gene, which encodes a nuclear receptor, result in growth retardation, congenital diaphragmatic hernia and congenital heart defects. Here, we show that <jats:italic>COUP<\/jats:italic>-<jats:italic>TFII<\/jats:italic> gene is expressed in the developing hypothalamus in mouse. The ventral forebrain-specific <jats:italic>RXCre<\/jats:italic>\/+; <jats:italic>COUP<\/jats:italic>-<jats:italic>TFII<\/jats:italic><jats:sup><jats:italic>F<\/jats:italic>\/<jats:italic>F<\/jats:italic><\/jats:sup> mutant mice display growth retardation. The development of the paraventricular nucleus of hypothalamus is compromised in the <jats:italic>COUP<\/jats:italic>-<jats:italic>TFII<\/jats:italic> mutant mainly because of increased apoptosis and mis-migration of the Brn2<jats:sup>+<\/jats:sup> neurons. Moreover, hypoplastic anterior pituitary with blood cell clusters and shrunken posterior pituitary lacking AVP\/OT neuron innervations are observed in the mutant, indicating the failure of formation of the hypothalamic-pituitary axis. Mechanistic studies show that the expression of <jats:italic>Bdnf<\/jats:italic> and <jats:italic>Nrp1<\/jats:italic> genes is reduced in the mutant embryo, and that <jats:italic>Bdnf<\/jats:italic> is a direct downstream target of the COUP-TFII protein. Thus, our findings provide a novel functional validation that <jats:italic>COUP<\/jats:italic>-<jats:italic>TFII<\/jats:italic> gene promotes the expression of <jats:italic>Bdnf<\/jats:italic> and <jats:italic>Nrp1<\/jats:italic> genes to ensure the appropriate morphogenesis of the hypothalamic-pituitary axis, especially the paraventricular nucleus of hypothalamus, and to prevent growth retardation.<\/jats:p>","DOI":"10.1038\/s41598-017-05682-6","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T09:42:32Z","timestamp":1499420552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII"],"prefix":"10.1038","volume":"7","author":[{"given":"Su","family":"Feng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingyu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunbo","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaoyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-0070","authenticated-orcid":false,"given":"Saber Mohamed","family":"Abd-Allah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naihe","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-4667","authenticated-orcid":false,"given":"Ke","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"5682_CR1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nature05026","volume":"443","author":"GJ Morton","year":"2006","unstructured":"Morton, G. 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