Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus
Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus
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DOI：
10.1210/me.2003-0372
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发表时间：
2004-05-01
影响因子：
--
通讯作者：
Fan, CM
中科院分区：
文献类型：
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作者：
Goshu, E;Jin, H;Fan, CM
下丘脑室旁核(PVN)和视上核通过调节垂体激素输出来维持动态平衡。室旁核和视上核含有五种主要细胞类型：催产素、加压素、促肾上腺皮质激素释放激素、生长抑素和促肾上腺皮质激素释放激素分泌神经元。Sim1、Arnt2和OTP基因对这些神经元的终末分化是必不可少的。它们共同的下游基因之一Brn2是催产素、加压素和CRH细胞分化所必需的。在此，我们发现SIM1的同源基因SIM2参与了视前背侧区、室旁前核和室旁核中TRH和SS基因的表达。Sim2的表达与表达TRH和SS的细胞重叠，并且Sim2突变体含有数量减少的TRH和SS细胞。在基因上，Sim1在Sim2的上游起作用，并部分补偿Sim2的丢失。早期下丘脑前部的比较表达研究表明，存在不同的TRH细胞池，其独特的分子密码由Sim1和Sim2的表达定义。结合以前的报道，我们的结果表明，Sim1和OTP利用两个共同的下游基因Brn2和Sim2来调节不同的神经内分泌激素基因表达。
Paraventricular (PVN) and supraoptic nuclei of the hypothalamus maintain homeostasis by modulating pituitary hormonal output. PVN and supraoptic nuclei contain five major cell types: oxytocin-, vasopressin-, CRH-, somatostatin-, and TRH-secreting neurons. Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons. One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation. Here we show that Sim2, a paralog of Sim1, contributes to the expression of Trh and Ss genes in the dorsal preoptic area, anterior-periventricular nucleus, and PVN. Sim2 expression overlaps with Trh- and Ss-expressing cells, and Sim2 mutants contain reduced numbers of Trh and Ss cells. Genetically, Sim1 acts upstream of Sim2 and partially compensates for the loss of Sim2. Comparative expression studies at the anterior hypothalamus at early stages reveal that there are separate pools of Trh cells with distinctive molecular codes defined by Sim1 and Sim2 expression. Together with previous reports, our results demonstrate that Sim1 and Otp utilize two common downstream genes, Brn2 and Sim2, to mediate distinctive sets of neuroendocrine hormone gene expression.