Single-cell transcriptomics of the early developing mouse cerebral cortex disentangles the spatial and temporal components of neuronal fate acquisition

Abstract

In the developing cerebral cortex, how progenitors that seemingly display limited diversity end up in producing a vast array of neurons remains a puzzling question. The prevailing model that recently emerged suggests that temporal maturation of these progenitors is a key driver in the diversification of the neuronal output. However, temporal constrains are unlikely to account for all diversity across cortical regions, especially in the ventral and lateral domains where neuronal types significantly differ from their dorsal neocortical counterparts born at the same time. In this study, we implemented single-cell RNAseq to sample the diversity of progenitors and neurons along the dorso-ventral axis of the early developing pallium. We first identified neuronal types, mapped them on the tissue and performed genetic tracing to determine their origin. By characterising progenitor diversity, we disentangled the gene expression modules underlying temporal vs spatial regulations of neuronal specification. Finally, we reconstructed the developmental trajectories followed by ventral and dorsal pallial neurons to identify gene waves specific of each lineage. Our data suggest a model by which discrete neuronal fate acquisition from a continuous gradient of progenitors results from the superimposition of spatial information and temporal maturation.