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

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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.