How is placental specific transcription factor GCMa/1 involved in development and maintanance of placenta?

胎盘特异性转录因子GCMa/1如何参与胎盘的发育和维持？

• 批准号: 15591786
• 负责人: OGAWA Hisamitsu
• 金额: $ 2.24万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591786/
• 关键词: GCMa; 1; placenta; transcription factor; monoclonal antibody; 妊娠中毒症; GCMタンパク質

The glial cell-missing (GCM) gene is the primary regulator of glial cell determination in the nervous system of Drosophila melanogaster. Two mammalian homologues have been identified. One of them, GCMa/1 is a transcription factor that solely expresses in the placenta. It is required for the development of syncytiotrophoblast that forms branching morphology of the placenta. Null-mutation of the factor results early embryonic death due to the placental failure.We tried to get mouse monoclonal antibodies against hGCMa/1. We obtained 2 clones that detected hGCMa/1 expressed in E coli and in insect cells. Authentic hGCMa/1 in normal term placenta and mGCMa/1 in mouse placenta were also recognized by the antibodies in Western blotting.We cloned a GCM ortholog from chicken. The new GCM ortholog (chGCM) is expressed only transiently during embryogenesis and is restricted exclusively to extra-embryonic tissue. To further compare the expression of chGCM to other GCM protein, we analyzed a set of organs from adult chicken. We failed to detected chGCM in thymus, which is the tissue known to expressed mouse GCMa postnatally. Intriguingly, chGCM was detected in adult ovaries, confirmed by Northern blotting. Taking the extraembryonic expression of chGCM and mammalian GCMa, it is tempting to speculate that a conserved extra-embryonic function exits for GCM protein in birds and mammals.We tried the expression of GCMa/1 gene in placenta of different gestational age as determined by quantitative real-time RT-PCR. GCMa/1 mRNA was constantly detected throughout the analyzed stages with slight decreases during the late third trimester.

神经胶质细胞缺失（GCM）基因是黑腹果蝇神经系统中神经胶质细胞决定的主要调控因子。已鉴定出两种哺乳动物同源物。其中，GCMa/1是一种仅在胎盘中表达的转录因子。它是形成胎盘分支形态的合体滋养细胞发育所必需的。该因子的零突变导致胎盘衰竭导致的早期胚胎死亡。我们试图获得抗hGCMa/1的小鼠单克隆抗体。我们获得了在大肠杆菌和昆虫细胞中检测到hGCMa/1的2个克隆。正常足月胎盘的hGCMa/1抗体和小鼠胎盘的mGCMa/1抗体也能被Western blotting识别。我们克隆了鸡的GCM同源基因。新的GCM同源物（chGCM）仅在胚胎发生期间短暂表达，并且仅限于胚胎外组织。为了进一步比较chGCM与其他GCM蛋白的表达，我们分析了一组成年鸡的器官。我们未能在胸腺中检测到chGCM，这是已知的小鼠出生后表达GCMa的组织。有趣的是，通过Northern blotting证实，成人卵巢中也检测到chGCM。结合chGCM和哺乳动物GCMa的胚胎外表达，我们很容易推测GCM蛋白在鸟类和哺乳动物中存在保守的胚胎外功能。采用实时荧光定量RT-PCR检测不同胎龄胎盘中GCMa/1基因的表达。GCMa/1 mRNA在整个分析阶段持续检测，在妊娠晚期略有下降。