Department of Functional Epigenetics in the Animal Model, Institute for Biology II, RWTH Aachen University, Worringerweg 3, 52074 Aachen, Germany.
Brain Res. 2018 Dec 1;1700:160-169. doi: 10.1016/j.brainres.2018.09.001. Epub 2018 Sep 4.
The proper function of the cerebral cortex relies on the delicate balance of excitation and inhibition determined by the accurate number and subtype composition of the diverse group of inhibitory gamma-aminobutyric (GABA)-expressing interneurons. Developmental defects can lead to impaired cortical inhibition and seem implicated in neuropsychiatric disorders like schizophrenia. The multifaceted development of cortical interneurons, of which the long-range migration from the basal telencephalon to cortical targets represents a critical step, is orchestrated by various intrinsic and extrinsic factors. Besides motogenic factors, neuronal activity determined by neurotransmitter and calcium signaling turned out as a crucial driver of cortical interneuron motility and migration, whereas the directionality is orchestrated by specific guidance receptors. Thereby, the responses towards different guidance and neurotransmitters cues appear highly stage and cell type- specific, relying on a complex transcriptional network that instruct the expression of particular receptor combinations. The contribution of epigenetic mechanisms to gene expression control that direct cortical interneuron migration and maturation are now beginning to be approached. This is key to decipher interneuron subtype-specific developmental programs and helps to understand how environmental signals can shape subtype-specific maturation. This review provides an overview about the achievements that were made in uncovering the regulatory networks orchestrating the migration of distinct cortical interneuron subtypes with focus on the role neuronal activity and epigenetic transcriptional control.
大脑皮层的正常功能依赖于兴奋和抑制之间的精细平衡，这种平衡由不同类型的抑制性γ-氨基丁酸（GABA）表达中间神经元的准确数量和亚型组成来决定。发育缺陷可导致皮质抑制受损，似乎与精神分裂症等神经精神疾病有关。皮质中间神经元的多方面发育受到各种内在和外在因素的调控，其中从基底端脑到皮质靶区的长距离迁移是一个关键步骤。除了运动因子外，由神经递质和钙信号决定的神经元活动也被证明是皮质中间神经元运动和迁移的关键驱动因素，而方向性则由特定的导向受体来协调。因此，对不同导向和神经递质线索的反应表现出高度的阶段和细胞类型特异性，这依赖于一个复杂的转录网络，该网络指导特定受体组合的表达。现在，人们开始研究表观遗传机制对指导皮质中间神经元迁移和成熟的基因表达调控的贡献。这对于解析中间神经元亚型特异性发育程序以及理解环境信号如何影响特定亚型的成熟至关重要。本文综述了在揭示调控不同皮质中间神经元亚型迁移的调控网络方面所取得的成就，重点介绍了神经元活动和表观遗传转录控制的作用。
