GSE161605
Single-cell transcriptomics of the early developing mouse cerebral cortex disentangles the spatial and temporal components of neuronal fate acquisition
The establishment of neuronal diversity in the developing cerebral cortex is currently the focus of much attention. 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 progenitors in the dorsal pallium is a key driver in the diversification of neuronal output. However, temporal constrains are unlikely to account for all diversity across pallial domains, especially in the ventral and lateral aspects where neurons that will later belong to the olfactory cortex, claustrum and amygdala significantly differ from their 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 pallium. We first identified neuronal types, mapped them on the tissue and performed genetic tracing to determine their ontogenic origin. We then investigated progenitor diversity and extensively characterized genes with variable expression along the dorso-ventral axis. We further identified those subjected to temporal vs spatial regulations. 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 in which discrete neuronal fate acquisition from a continuous gradient of progenitors results from probabilistic mechanisms with a strong bias imposed on progenitors by both spatial information and temporal maturation. Overall design: We applied scRNAseq profiling on dissected E12.5 mouse cortex containing subpallial as well as ventral, lateral and dorsal pallial cells