A role of the LIM-homeobox gene Lhx2 in the regulation of pituitary development.

A role of the LIM-homeobox gene Lhx2 in the regulation of pituitary development.
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DOI:
10.1016/j.ydbio.2009.11.002
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发表时间:
2010-01-15
影响因子:
2.7
通讯作者:
Westphal, Heiner
Westphal, Heiner
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao, Yangu;Mailloux, Christina M.;Hermesz, Edit;Palkovits, Miklos;Westphal, Heiner

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哺乳动物的脑下垂体起源于胚胎发育过程中的两个独立的生发组织。垂体腺的前叶和中间叶来源于Rathke囊,Rathke囊是由口腔外胚层内陷形成的袋。后叶起源于漏斗,漏斗由腹侧间脑内的神经外胚层外翻形成。以前的研究表明,Rathke氏囊的发育和垂体前/中间叶中不同群体产生激素的内分泌细胞系的产生受该囊中表达的一系列转录因子和腹侧间脑/漏斗的诱导信号的调控。然而,人们对调节垂体后叶发育的因素知之甚少。在本研究中,我们发现LIM-Homeobox基因LHX2在发育中的腹侧间脑中广泛表达,包括漏斗和垂体后叶。LHX2基因缺失导致细胞持续增殖,腹侧间脑神经外胚层完全外翻,漏斗和垂体后叶形成明显的形态特征。在LHX2突变体的前/中间垂体叶中形成了Rathke囊和内分泌细胞谱系。然而,由于漏斗和后叶发育缺陷,脑袋和前/中间垂体叶的形状和组织发生了严重变化。因此,我们的研究揭示了LHX2在调节垂体后叶发育中的重要作用,并提出了一种机制,即后叶的发育可能影响垂体前叶和中间叶的发育。
The mammalian pituitary gland originates from two separate germinal tissues during embryonic development. The anterior and intermediate lobes of the pituitary are derived from Rathke's pouch, a pocket formed by an invagination of the oral ectoderm. The posterior lobe is derived from the infundibulum, which is formed by evagination of the neuroectoderm in the ventral diencephalon. Previous studies have shown that development of Rathke's pouch and the generation of distinct populations of hormone-producing endocrine cell lineages in the anterior/intermediate pituitary lobes is regulated by a number of transcription factors expressed in the pouch and by inductive signals from the ventral diencephalon/infundibulum. However, little is known about factors that regulate the development of the posterior pituitary lobe. In this study, we show that the LIM-homeobox gene Lhx2 is extensively expressed in the developing ventral diencephalon, including the infundibulum and the posterior lobe of the pituitary. Deletion of Lhx2 gene results in persistent cell proliferation, a complete failure of evagination of the neuroectoderm in the ventral diencephalon, and defects in the formation of the distinct morphological features of the infundibulum and the posterior pituitary lobe. Rathke's pouch is formed and endocrine cell lineages are generated in the anterior/intermediate pituitary lobes of the Lhx2 mutant. However, the shape and organization of the pouch and the anterior/intermediate pituitary lobes are severely altered due to the defects in development of the infundibulum and the posterior lobe. Our study thus reveals an essential role for Lhx2 in the regulation of posterior pituitary development and suggests a mechanism whereby development of the posterior lobe may affect the development of the anterior and intermediate lobes of the pituitary gland.
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