Lamolet Bruno, Poulin Gino, Chu Khoi, Guillemot François, Tsai Ming-Jer, Drouin Jacques
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada H2W 1R7.
Mol Endocrinol. 2004 Apr;18(4):995-1003. doi: 10.1210/me.2003-0127. Epub 2004 Jan 15.
NeuroD1(BETA2) and Tpit are cell-specific activators of pituitary proopiomelanocortin (POMC) gene transcription. Expression of both factors slightly precedes that of POMC at embryonic d 12.5 of mouse pituitary development. We now report that NeuroD1(BETA2) is required for early corticotroph differentiation. In agreement with the transcriptional synergism observed between Tpit and basic helix-loop-helix dimers containing NeuroD1(BETA2), POMC expression is delayed in NeuroD1-deficient mice. However, this differentiation defect does not reflect a change of corticotroph commitment as revealed by Tpit expression. The delay of corticotroph terminal differentiation is transient and coincides with the developmental window of NeuroD1 expression in corticotrophs. In contrast to their requirement in other NeuroD1-expressing cells, the neurogenin genes do not appear to be necessary for corticotroph differentiation. Taken together with a similar requirement of Tpit for corticotroph differentiation but not for commitment, the present data indicate that the POMC promoter is a point of convergence for independent corticotroph differentiating signals.
神经分化因子1（NeuroD1，即β2）和垂体特异性转录因子（Tpit）是垂体阿黑皮素原（POMC）基因转录的细胞特异性激活因子。在小鼠垂体发育的胚胎第12.5天，这两种因子的表达略早于POMC的表达。我们现在报告，神经分化因子1（NeuroD1，即β2）是早期促肾上腺皮质激素细胞分化所必需的。与在Tpit和含有神经分化因子1（NeuroD1，即β2）的碱性螺旋-环-螺旋二聚体之间观察到的转录协同作用一致，POMC在神经分化因子1缺陷小鼠中的表达延迟。然而，这种分化缺陷并不反映促肾上腺皮质激素细胞的定向改变，这一点由Tpit的表达得以揭示。促肾上腺皮质激素细胞终末分化的延迟是短暂的，并且与促肾上腺皮质激素细胞中神经分化因子1表达的发育窗口一致。与它们在其他表达神经分化因子1的细胞中的需求相反，神经生成素基因似乎对促肾上腺皮质激素细胞的分化不是必需的。结合Tpit对促肾上腺皮质激素细胞分化而非定向有类似需求，目前的数据表明POMC启动子是独立的促肾上腺皮质激素细胞分化信号的汇聚点。
