Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII

Abstract The paraventricular nucleus of hypothalamus plays important roles in the regulation of energy balance and fetal growth. However, the molecular mechanisms underlying its formation and function have not been clearly elucidated. Various mutations in the human COUP-TFII gene, which encodes a nu...

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Autores principales:	Su Feng, Can Xing, Tingyu Shen, Yunbo Qiao, Ran Wang, Jun Chen, Jiaoyang Liao, Zhuo Lu, Xiong Yang, Saber Mohamed Abd-Allah, Jinsong Li, Naihe Jing, Ke Tang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e846594bb85b4f30b9afb0526de6bfa1
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spelling	oai:doaj.org-article:e846594bb85b4f30b9afb0526de6bfa12021-12-02T15:05:27ZAbnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII10.1038/s41598-017-05682-62045-2322https://doaj.org/article/e846594bb85b4f30b9afb0526de6bfa12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05682-6https://doaj.org/toc/2045-2322Abstract The paraventricular nucleus of hypothalamus plays important roles in the regulation of energy balance and fetal growth. However, the molecular mechanisms underlying its formation and function have not been clearly elucidated. Various mutations in the human COUP-TFII gene, which encodes a nuclear receptor, result in growth retardation, congenital diaphragmatic hernia and congenital heart defects. Here, we show that COUP-TFII gene is expressed in the developing hypothalamus in mouse. The ventral forebrain-specific RXCre/+; COUP-TFII F/F mutant mice display growth retardation. The development of the paraventricular nucleus of hypothalamus is compromised in the COUP-TFII mutant mainly because of increased apoptosis and mis-migration of the Brn2+ 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 Bdnf and Nrp1 genes is reduced in the mutant embryo, and that Bdnf is a direct downstream target of the COUP-TFII protein. Thus, our findings provide a novel functional validation that COUP-TFII gene promotes the expression of Bdnf and Nrp1 genes to ensure the appropriate morphogenesis of the hypothalamic-pituitary axis, especially the paraventricular nucleus of hypothalamus, and to prevent growth retardation.Su FengCan XingTingyu ShenYunbo QiaoRan WangJun ChenJiaoyang LiaoZhuo LuXiong YangSaber Mohamed Abd-AllahJinsong LiNaihe JingKe TangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Su Feng Can Xing Tingyu Shen Yunbo Qiao Ran Wang Jun Chen Jiaoyang Liao Zhuo Lu Xiong Yang Saber Mohamed Abd-Allah Jinsong Li Naihe Jing Ke Tang Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
description	Abstract The paraventricular nucleus of hypothalamus plays important roles in the regulation of energy balance and fetal growth. However, the molecular mechanisms underlying its formation and function have not been clearly elucidated. Various mutations in the human COUP-TFII gene, which encodes a nuclear receptor, result in growth retardation, congenital diaphragmatic hernia and congenital heart defects. Here, we show that COUP-TFII gene is expressed in the developing hypothalamus in mouse. The ventral forebrain-specific RXCre/+; COUP-TFII F/F mutant mice display growth retardation. The development of the paraventricular nucleus of hypothalamus is compromised in the COUP-TFII mutant mainly because of increased apoptosis and mis-migration of the Brn2+ 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 Bdnf and Nrp1 genes is reduced in the mutant embryo, and that Bdnf is a direct downstream target of the COUP-TFII protein. Thus, our findings provide a novel functional validation that COUP-TFII gene promotes the expression of Bdnf and Nrp1 genes to ensure the appropriate morphogenesis of the hypothalamic-pituitary axis, especially the paraventricular nucleus of hypothalamus, and to prevent growth retardation.
format	article
author	Su Feng Can Xing Tingyu Shen Yunbo Qiao Ran Wang Jun Chen Jiaoyang Liao Zhuo Lu Xiong Yang Saber Mohamed Abd-Allah Jinsong Li Naihe Jing Ke Tang
author_facet	Su Feng Can Xing Tingyu Shen Yunbo Qiao Ran Wang Jun Chen Jiaoyang Liao Zhuo Lu Xiong Yang Saber Mohamed Abd-Allah Jinsong Li Naihe Jing Ke Tang
author_sort	Su Feng
title	Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
title_short	Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
title_full	Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
title_fullStr	Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
title_full_unstemmed	Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
title_sort	abnormal paraventricular nucleus of hypothalamus and growth retardation associated with loss of nuclear receptor gene coup-tfii
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e846594bb85b4f30b9afb0526de6bfa1
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Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII

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