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

糖皮质激素在人体内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，以维持健康和福祉。众所周知，糖皮质激素功能失调会增加患上严重抑郁、焦虑和创伤后应激障碍等精神健康障碍的易感性。然而，目前这些糖皮质激素对大脑影响的分子基础仍然不清楚。研究最多的大脑结构是海马体，因为它在应对压力以及学习和记忆过程中扮演着重要角色。糖皮质激素通过与两个细胞内受体--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，这两个受体的作用类似于配体依赖的转录因子。最近，我们在海马区进行了所谓的染色质免疫沉淀(ChIP)分析，以首次确定MR和GR在基线和应激条件下相互作用的基因(参见Mifsud&Reul(2016)Proc)。娜塔莉。阿卡德。SCI。USA113：11336-41；Mifsud等人。(2021)自然通讯12：4737)。在众多发现中，我们发现MR尤其与神经元分化和纤毛功能有关。纤毛是包括神经元在内的细胞的毛发状突起，在感觉和发育过程中发挥关键作用。神经元分化和纤毛发生都是发生在海马齿状回的成年神经发生过程的一部分，齿状回是海马区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了作用，但目前还不清楚具体是如何发生的。我们能够证实MR对于人类胚胎神经前体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，MR很可能在基因组上与所谓的调节因子X(RFX)因子相互作用，这些因子对纤毛发生至关重要。这些新的发现为深入研究MR和RFX因子之间的联系提供了坚实的理论基础和基础，这些因子与神经元分化和纤毛发生有关，是胚胎和成人神经发生过程的一部分。

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.