Interaction of Regulatory Factor X (RFX) factors and the mineralocorticoid receptor (MR) in neuronal differentiation and ciliogenesis in embryonic an

糖皮质激素在人体中起着非常重要的功能作用。它们调节新陈代谢、免疫系统以及许多大脑功能，以维持健康和幸福。众所周知，糖皮质激素功能失调会增加患重度抑郁症、焦虑症和创伤后应激障碍等精神健康障碍的风险。然而，目前，糖皮质激素对大脑影响的分子基础仍未被阐明。研究最多的大脑结构是海马体，因为它在压力应对和学习记忆过程中起作用。糖皮质激素通过与两种细胞内受体（矿盐皮质激素受体（MR）和糖皮质激素受体（GR））相互作用作用于海马体，这两种受体类似于配体依赖性转录因子。最近，我们对海马进行了所谓的染色质免疫沉淀（ChIP）分析，首次鉴定了在基线和应激条件下MR和GR相互作用的基因（见Mifsud & Reul (2016) Proc. Natl）。学会科学。美国113:11336-41;Mifsud et al. (2021) Nature Communications 12: 4737)。在许多发现中，我们发现，特别是MR，参与神经元分化和纤毛功能。纤毛是细胞（包括神经元）上的毛发状突起，在感觉和发育过程中起着关键作用。神经元分化和纤毛发生都是成人神经发生过程的一部分，发生在齿状回，海马体的一个高度可塑性的区域。事实上，MR被认为在齿状神经发生的神经元分化阶段发挥作用，但具体如何发挥作用目前尚不清楚。我们能够证实MR对人类胎儿神经祖细胞的神经元分化和纤毛发生至关重要（hfnpc； Mifsud等人，2021）。我们还发现，很可能在基因组中，MR与所谓的调节因子X （RFX）因子相互作用，这对纤毛发生至关重要。这些新发现为深入研究MR和RFX因子在胚胎和成人神经发生过程中与神经元分化和纤毛发生相关的联系提供了坚实的理论基础。

Glucocorticoid hormones play very important functional roles in the body. They regulate metabolism, the immune system as well as many brain functions to maintain health and wellbeing. Dysregulation of glucocorticoid hormone function is known to enhance vulnerability for developing mental health disorders like major depression, anxiety and post-traumatic stress disorder. Presently, however, the molecular underpinnings of these glucocorticoid effects on the brain have still not been clarified. The brain structure mostly investigated is the hippocampus because of its role in stress coping and learning and memory processes. Glucocorticoid hormones act on the hippocampus through interaction with two intracellular receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), which act like ligand-dependent transcription factors. Recently, we conducted so-called chromatin immunoprecipitation (ChIP) analysis on the hippocampus to identify, for the first time, the genes with which MR and GR interact under baseline and stress conditions (see Mifsud & Reul (2016) Proc. Natl. Acad. Sci. USA 113:11336-41; Mifsud et al. (2021) Nature Communications 12: 4737). Amongst many findings, we discovered that, the MR in particular, is involved in neuronal differentiation and cilia function. Cilia are hair-like protrusions from cells, including neurons, that play critical roles in sensory and developmental processes. Both neuronal differentiation and ciliogenesis are part of the adult neurogenesis process taking place in the dentate gyrus, a highly plastic region of the hippocampus. Indeed, MR is thought to play a role in the neuronal differentiation phase of dentate neurogenesis but exactly how is presently unknown. We were able to confirm that MR is critical for neuronal differentiation and ciliogenesis in human foetal neuronal progenitor cells (hfNPCs; Mifsud et al., 2021). We also discovered that, most likely at the genome, MR interacts with so called Regulatory Factor X (RFX) factors, which are critical for ciliogenesis. These novel findings provide a solid rationale and basis for the in-depth investigation of the connection between MR and RFX factors in relation to neuronal differentiation and ciliogenesis as part of the embryonic and adult neurogenesis process.