Mechanism of adrenocortical development

肾上腺皮质通过合成盐皮质激素和糖皮质激素，对体内离子和葡萄糖浓度的平衡起着至关重要的作用，而核受体超家族成员Ad4BP/SF-1在肾上腺皮质的发育和类固醇基因调控中起着重要作用。为了阐明组织发育的机制，我们鉴定了Ad4BP/SF-1基因的肾上腺特异性增强子，并检测了肾上腺特异性表达所需的核苷酸序列的功能。随后，我们研究了与功能序列结合的转录因子。结果发现，Hox/Pbx/Meis复合物通过结合激活增强子功能，并讨论了胎儿肾上腺皮质和成人肾上腺皮质起源于不同的细胞。我们目前的研究发现，肾上腺特异性增强子仅在胎儿而非成人肾上腺皮质中驱动基因表达。使用增强子，我们产生了Cre重组酶转基因在胎儿肾上腺中特异性诱导的小鼠。将小鼠与ROSA小鼠杂交以标记其中胎儿肾上腺增强子开启一次的细胞，并检查细胞的细胞谱系。因此，我们证明了胎儿肾上腺皮质的某些群体具有分化成成人肾上腺皮质的潜力，并且这种分化能力可以在组织的早期阶段被检测到，此后很快消失。

The adrenal cortex plays a crucial role for homeostasis of ionic and glucose concentration through synthesis of mineralocorticoid and glucocorticoid, while Ad4BP/SF-1, a member of nuclear receptor superfamily, plays roles for development and steroidogenic gene regulation of the adrenal cortex. In order to elucidate the mechanism for the tissue development, we identified adrenal specific enhancer of Ad4BP/SF-1 gene and examined the function of the nucleotide sequences required for the adrenal specific expression. Subsequently, we investigated the transcription factors which bind to the functional sequences. As the consequence, we found that Hox/Pbx/Meis complex activates enhancer function through binding.It has been discussed that the fetal adrenal cortex and adult adrenal cortex originate from mutually distinct cells. The adrenal specific enhancer identified by our current study drives gene expression only in the fetal but not adult adrenal cortex. Using the enhancer, we produced mice in which Cre recombinase transgene is induced specifically in the fetal adrenal. The mice were crossed with ROSA mice to label the cells in which the fetal adrenal enhancer turned on once, and examined cell lineage of the cells. As the consequence, we demonstrated that a certain population of the fetal adrenal cortex has the potential to differentiate into the adult adrenal cortex, and this ability for differentiation can be detected at an early stage of the tissue and thereafter disappears soon.