Abnormal Epithelial Cell Polarity and Ectopic Epidermal Growth Factor Receptor (EGFR) Expression Induced in Emx2 KO Embryonic Gonads
Abnormal Epithelial Cell Polarity and Ectopic Epidermal Growth Factor Receptor (EGFR) Expression Induced in Emx2 KO Embryonic Gonads
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DOI：
10.1210/en.2010-0915
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Morohashi, Ken-ichirou
中科院分区：
文献类型：
--
作者：
Kusaka, Masatomo;Katoh-Fukui, Yuko;Morohashi, Ken-ichirou
性腺原基首先作为胚胎体腔上皮的增厚而出现，人们认为它向内侧迁移形成原始性腺。然而，早期性腺发育仍然知之甚少。缺乏配对样同源盒基因 Emx2 的小鼠表现出性腺发育不全。有趣的是，敲除（KO）胚胎性腺发育出不寻常的表面，并伴有异常的紧密连接组装。形态学和体外细胞命运图谱研究表明，KO 中迁移至间充质室的性腺上皮细胞数量明显减少，表明极化细胞分裂和随后的细胞迁移受到影响。上皮细胞的微阵列分析显示 KO 中 Egfr 显着上调，表明 Emx2 抑制 Egfr 基因表达。这两个基因之间的遗传相关性通过培养的中肾上皮细胞衍生的 M15 细胞重现。最近显示表皮生长因子受体信号传导通过肉瘤病毒癌基因同源物酪氨酸磷酸化来调节紧密连接组装。我们通过 Emx2 KO 分析表明，肉瘤病毒癌基因同源物酪氨酸磷酸化、表皮生长因子受体酪氨酸磷酸化和 Egfr 表达在胚胎性腺中上调。我们的结果强烈表明，Emx2 是调节紧密连接组装和允许性腺上皮迁移至间充质所必需的，这可能是通过抑制 Egfr 表达来介导的。 （内分泌学151：5893-5904，2010）
The gonadal primordium first emerges as a thickening of the embryonic coelomic epithelium, which has been thought to migrate mediodorsally to form the primitive gonad. However, the early gonadal development remains poorly understood. Mice lacking the paired-like homeobox gene Emx2 display gonadal dysgenesis. Interestingly, the knockout (KO) embryonic gonads develop an unusual surface accompanied by aberrant tight junction assembly. Morphological and in vitro cell fate mapping studies showed an apparent decrease in the number of the gonadal epithelial cells migrated to mesenchymal compartment in the KO, suggesting that polarized cell division and subsequent cell migration are affected. Microarray analyses of the epithelial cells revealed significant up-regulation of Egfr in the KO, indicating that Emx2 suppresses Egfr gene expression. This genetic correlation between the two genes was reproduced with cultured M15 cells derived from mesonephric epithelial cells. Epidermal growth factor receptor signaling was recently shown to regulate tight junction assembly through sarcoma viral oncogene homolog tyrosine phosphorylation. We show through Emx2 KO analyses that sarcoma viral oncogene homolog tyrosine phosphorylation, epidermal growth factor receptor tyrosine phosphorylation, and Egfr expression are up-regulated in the embryonic gonad. Our results strongly suggest that Emx2 is required for regulation of tight junction assembly and allowing migration of the gonadal epithelia to the mesenchyme, which are possibly mediated by suppression of Egfr expression. (Endocrinology 151: 5893-5904, 2010)