Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke's pouch and increases cell apoptosis during mouse pituitary development.
Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke's pouch and increases cell apoptosis during mouse pituitary development.
复制标题
LIM-同源盒基因 Lhx3 表达的减少会损害 Rathke 囊的生长和分化，并增加小鼠垂体发育过程中的细胞凋亡。
DOI：
10.1016/j.mod.2006.06.005
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发表时间：
2006
影响因子：
2.6
通讯作者：
Westphal,Heiner
中科院分区：
文献类型：
--
作者：
Zhao,Yangu;Morales,DonnaChelle;Hermesz,Edit;Lee,Woon-Kyu;Pfaff,SamuelL;Westphal,Heiner
垂体前叶和中叶的形成是一个多步骤的过程，受涉及许多信号通路的细胞间相互作用和细胞内在转录因子级联的调节。LIM-homeodoamin蛋白Lhx 3先前已被证明在Rathke囊（垂体前叶和中叶的原基）的生长中起重要作用。然而，Lhx 3的功能和调节机制仍有待阐明。在这里，我们报告了在Lhx 3基因的3′-非翻译区靶向插入一个DNA片段，降低了Rathke囊中Lhx 3 mRNA和蛋白的表达。这种Lhx 3等位基因纯合子的突变小鼠表现出严重的发育不全的邮袋，缺陷相同的Lhx 3无效突变体中观察到的。为了深入了解Lhx 3在垂体发育中的功能机制，我们通过检查早期垂体标志物表达、细胞增殖和细胞凋亡进一步分析了Lhx 3缺陷突变体。我们的研究结果显示，这些突变体的Rathke囊中细胞凋亡增加，Islet 1和Calbindin标记物表达丧失。最近，增加细胞凋亡的Rathke袋已被描述在突变小鼠的功能受损的bicoid样同源结构域蛋白Pitx 1和Pitx 2。在这些突变体中，Lhx 3的表达缺失。因此，我们的研究结果强调了这样的观点，即Lhx 3的功能下游的Pitx因子在相同的转录级联，控制生长和早期细胞分化的发展中的垂体。
The formation of the anterior and intermediate lobes of the pituitary gland is a multi-step process regulated by cell–cell interactions involving a number of signaling pathways and by cascades of cell-intrinsic transcription factors. The LIM-homeodoamin protein Lhx3 has previously been shown to play an essential role in the growth of Rathke’s pouch, a primordium of the anterior and intermediate lobes of the pituitary. However, the mechanisms underlying the function and regulation of Lhx3 remain to be elucidated. Here we report that a targeted insertion of a DNA fragment in the 3′-untranslated region of the Lhx3 gene reduces the expression of both Lhx3 mRNA and protein in Rathke’s pouch. Mutant mice homozygous for this Lhx3 allele show severe hypoplasia of the pouch, a defect identical to that observed in Lhx3-null mutants. To gain insights into the mechanism of Lhx3 function in pituitary development, we further analyzed the Lhx3 deficient mutants by examination of early pituitary marker expression, cell proliferation, and cell apoptosis. Our results revealed an increase in cell apoptosis and a loss of Islet1 and Calbindin marker expression in Rathke’s pouch of these mutants. Recently, increased cell apoptosis in Rathke’s pouch has been described in mutant mice impaired in the function of the bicoid-like homeodomain proteins Pitx1 and Pitx2. In those mutants, the expression of Lhx3 is absent. Our results thus underscore the view that Lhx3 functions downstream of the Pitx factors in the same transcriptional cascade that controls growth and early cell differentiation of the developing pituitary gland.