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Role of transcription factors and a differentiation inhibiting factor which concern differentiation of a common primordiam of adrenal cortex and gonad.

转录因子和分化抑制因子的作用涉及肾上腺皮质和性腺的共同原基的分化。

基本信息

批准号：
12680720
负责人：
HATANO Osamu
金额：
$ 2.24万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680720/
关键词：
Ad4BP SF-1 Pref-1 WT1 Emx2 Adrenal Cortex Gonad Development Organogenesis 副腎皮質生殖腺器官形成 As4BP WT-1 胚発生

项目摘要

Our previous study on expression profiles of Ad4BP/SF-1 in rat embryos demonstrated that steroid hormone-producing cells of adrenal cortex and gonads are derived from a common precursor named "adreno-genital primordium". The analysis of differentiation process of the primordium revealed that it consists of four steps. The aim of this project is to seek molecules which control differentiation of the adreno-genita primordium and examine the role of the factors. It was suggested that Pref-1/ZOG, WT1 , Emx2 and Ad4BP/SF-1 are the factors that control the differentiation of the adreno-genital primordium. Pref-1/ZOG was already expressed in the adreno-genital primordium and continued to be expressed only in the adrenocortical primordium but not in the gonadal primordium (=indifferent gonad). WT1 was expressed in the gonadal primordium, but not in the adrenocortical primordium. Analyses of Pref-1 gene promoter with co-transfection assays have shown that WT1 down-regulates the transcription of Pref-1 gene. On the other hands, Emx2-deficient mice fails to form gonads, but was not affected to form adrenal glands, suggesting that Emx2 acts in a different manner in the process of differentiation of the adreno-genital primordium. Emx2 also functions in the differentiation of brain. Using Emx2- and/or Emx1-deficient mice and anti-Emx2 antibody, we examined the role of Emx2 in the differentiation of brain and also in regeneration process of neural precursor cells after ischemic brain injury.

我们前期对Ad 4 BP/SF-1在大鼠胚胎中表达谱的研究表明，肾上腺皮质和性腺的类固醇激素产生细胞来源于一个共同的前体，称为“肾上腺-生殖原基”。对原基分化过程的分析表明，原基分化过程包括四个步骤。本研究的目的是寻找控制肾上腺素原基分化的分子，并研究这些因子的作用。提示Pref-1/ZOG、WT 1、Emx 2和Ad 4 BP/SF-1是控制肾上腺生殖原基分化的因子。Pref-1/ZOG已经在肾上腺-生殖器原基中表达，并且仅在肾上腺皮质原基中继续表达，但在性腺原基中不表达（=无关性腺）。WT 1在性腺原基中表达，在肾上腺皮质原基中不表达。通过共转染实验对Pref-1基因启动子的分析表明，WT 1下调Pref-1基因的转录。另一方面，Emx 2缺陷小鼠不能形成性腺，但不影响形成肾上腺，这表明Emx 2在肾上腺生殖原基分化过程中以不同的方式起作用。Emx 2还在脑的分化中起作用。利用Emx 2和/或Emx 1缺陷小鼠和抗Emx 2抗体，我们研究了Emx 2在脑分化和缺血性脑损伤后神经前体细胞再生过程中的作用。