Rptor/mTORC1 function in radial glia progenitor lineage progression

The cerebral cortex is composed of an extraordinary number of neuronal and glial cell types assembling into cortical circuits that account for cognitive abilities. Remarkable heterogeneity in the spectrum of cortical cell types has been described on the basis of global transcriptome analysis. How cell-type diversity is generated by radial glia progenitor (RGP) cells during development is however still poorly understood. Here we focus on the Rptor/mTORC1 signaling pathway and its role in RGP cell lineage progression and cortical neurogenesis. By using Mosaic Analysis with Double Markers (MADM) technology we ablated Rptor/mTORC1 either sparsely in single clones or in the entire tissue. Such paradigms enabled us to determine the relative contributions of cell-autonomous Rptor/mTORC1 function and their interaction with global tissue-wide mechanisms. We found that Rptor is not cell-autonomously required for cortical neurogenesis but rather for survival of defined populations of cortical excitatory neurons. Strikingly, RNA sequencing analysis unveiled differential requirement for Rptor function across distinct projection neuron classes, implying that mTORC1 signaling fulfills critical roles in the generation of cortical cell-type diversity.