miR-137 and miR-122, two outer subventricular zone non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation

• Published in: Cell reports (Cambridge) 2022-02, Vol.38 (7), p.110381-110381, Article 110381
• Main Authors: Tomasello, Ugo, Klingler, Esther, Niquille, Mathieu, Mule, Nandkishor, Santinha, Antonio J., de Vevey, Laura, Prados, Julien, Platt, Randall J., Borrell, Victor, Jabaudon, Denis, Dayer, Alexandre
• Format: Article
• Language: English
• Subjects: Animals; basal progenitors; Cell Differentiation - genetics; Cell Proliferation - genetics; Cellular Reprogramming - genetics; cortex; evolution; Ferrets; HEK293 Cells; Humans; Lateral Ventricles; Mice; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Mitosis - genetics; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; neurogenesis; Neurogenesis - genetics; neuronal maturation; Neurons - cytology; Neurons - metabolism; RNA, Untranslated - genetics; RNA, Untranslated - metabolism
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •oSVZ-expressed microRNAs 137 and 122 promote superficial layer identity of neurons•miR-137 promotes basal progenitor proliferation and layer 2/3 neuron generation•miR-122 slows down neuronal differentiation pace Tomasello et al. demonstrate the role of two microRNAs (miRNAs) during cortical expansion. miR-137 induces proliferative behavior on basal progenitors in the subventricular zone (SVZ), and miR-122 slows down excitatory neuron differentiation progression. These distinct but complementary processes amplify the generation and molecular acquisition of layer 2/3 excitatory neurons.