PITX genes are required for cell survival and Lhx3 activation
PITX genes are required for cell survival and Lhx3 activation
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DOI：
10.1210/me.2005-0052
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发表时间：
2005-07-01
影响因子：
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通讯作者：
Gage, PJ
中科院分区：
文献类型：
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作者：
Charles, MA;Suh, H;Gage, PJ
转录因子PITX家族调节许多器官的发育。Pitx1突变体有一个温和的垂体表型，但Pitx2是必要的发展Rathke的袋，表达的基本转录因子在促性腺激素，和扩展的Pit1谱系。我们报告说，缺乏Pitx2的原因袋进行过度的细胞死亡，导致严重的垂体发育不全。垂体中PITX2的转基因过表达可增加促性腺激素细胞群，表明PITX2的绝对浓度对于正常垂体细胞谱系扩增是重要的。我们发现，PITX1和PITX2蛋白在整个垂体发育和成熟垂体中以相似的表达模式存在。这两种转录因子优先表达在成人促性腺激素细胞和促甲状腺激素细胞，这表明在这些细胞类型的成人垂体功能的维护重叠的可能性。Pitx1和Pitx2的双敲除表现出严重的垂体发育不全，并且不能表达转录因子LHX 3。这表明这些PITX基因位于Lhx3的上游，在发育过程中具有补偿作用。因此，这些PITX家族成员的组合剂量对垂体发育至关重要，并且它们在成年垂体中的持续共表达表明在维持垂体功能中的持续作用。
The PITX family of transcription factors regulate the development of many organs. Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, and expansion of the Pit1 lineage. We report that lack of Pitx2 causes the pouch to undergo excessive cell death, resulting in severe pituitary hypoplasia. Transgenic overexpression of PITX2 in the pituitary can increase the gonadotrope population, suggesting that the absolute concentration of PITX2 is important for normal pituitary cell lineage expansion. We show that PITX1 and PITX2 proteins are present in similar expression patterns throughout pituitary development and in the mature pituitary. Both transcription factors are preferentially expressed in adult gonadotropes and thyrotropes, suggesting the possibility of overlap in maintenance of adult pituitary functions within these cell types. Double knockouts of Pitx1 and Pitx2 exhibit severe pituitary hypoplasia and fail to express the transcription factor LHX3. This indicates that these PITX genes are upstream of Lhx3 and have compensatory roles during development. Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function.