Ugo Tomasello, Esther Klingler, Mathieu Niquille, Nandkishor Mule, Antonio J. Santinha, Laura de Vevey, Julien Prados, Randall J. Platt, Victor Borrell, Denis Jabaudon, Alexandre Dayer, Swiss National Science Foundation, Brain and Behavior Research Foundation, European Research Council, EMBO, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), and Agencia Estatal de Investigación (España)
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., Cell Reports, 38 (7), ISSN:2666-3864, ISSN:2211-1247