Department of Basic Neurosciences, University of Geneva, 1205 Geneva, Switzerland; Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d'Alacant, 03550 Alacant, Spain.
Department of Basic Neurosciences, University of Geneva, 1205 Geneva, Switzerland.
Cell Rep. 2022 Feb 15;38(7):110381. doi: 10.1016/j.celrep.2022.110381.
Cortical expansion in primate brains relies on enlargement of germinal zones during a prolonged developmental period. Although most mammals have two cortical germinal zones, the ventricular zone (VZ) and subventricular zone (SVZ), gyrencephalic species display an additional germinal zone, the outer subventricular zone (oSVZ), which increases the number and diversity of neurons generated during corticogenesis. How the oSVZ emerged during evolution is poorly understood, but recent studies suggest a role for non-coding RNAs, which allow tight genetic program regulation during development. Here, using in vivo functional genetics, single-cell RNA sequencing, live imaging, and electrophysiology to assess progenitor and neuronal properties in mice, we identify two oSVZ-expressed microRNAs (miRNAs), miR-137 and miR-122, which regulate key cellular features of cortical expansion. miR-137 promotes basal progenitor self-replication and superficial layer neuron fate, whereas miR-122 decreases the pace of neuronal differentiation. These findings support a cell-type-specific role of miRNA-mediated gene expression in cortical expansion.
灵长类动物大脑的皮层扩张依赖于在一个延长的发育期间生殖区的扩大。虽然大多数哺乳动物有两个皮层生殖区，脑室区（VZ）和室下区（SVZ），但是脑回形成的物种显示出额外的生殖区，即外室下区（oSVZ），这增加了皮质发生过程中产生的神经元的数量和多样性。oSVZ 在进化过程中是如何出现的还不太清楚，但最近的研究表明非编码 RNA 在其中发挥了作用，非编码 RNA 允许在发育过程中进行紧密的遗传程序调控。在这里，我们使用体内功能遗传学、单细胞 RNA 测序、活体成像和电生理学来评估小鼠中祖细胞和神经元的特性，我们确定了两个 oSVZ 表达的 microRNA（miRNA），miR-137 和 miR-122，它们调节皮质扩张的关键细胞特征。miR-137 促进基底祖细胞的自我复制和浅层神经元命运，而 miR-122 则降低神经元分化的速度。这些发现支持 miRNA 介导的基因表达在皮质扩张中的细胞类型特异性作用。
