Temporal transcriptomic dynamics in developing macaque neocortex

Abstract Despite intense research focus in mice, the transcriptional regulation of neocortical neurogenesis remains limited in humans and non-human primates. Cortical development in rhesus macaque is known to recapitulate multiple facets cortical development in humans, including the complex composition of neural stem cells and thicker upper-layer neurons. To characterize temporal shifts in transcriptomic programming responsible for differentiation from stem cells to neurons, we sampled parietal lobes of rhesus macaque at E40, E50, E70, E80, and E90, spanning the full period of embryonic neurogenesis. Single cell RNA sequencing produced a transcriptomic atlas of the developing rhesus macaque neocortex parietal lobe. Identification of distinct cell types and neural stem cells emerging in different developmental stages revealed a terminally bifurcating trajectory from stem cells to neurons. Notably, deep-layer neurons appear in early stages of neurogenesis while upper-layer neurons appear later. While these different lineages show overlap in their differentiation program, cell fates are determined post-mitotically. Pseudotime trajectories from vRGs to oRGs revealed differences in dynamic gene expression profiles, and identified divergence in their activation of BMP, FGF, and WNT signaling pathways. These results provide a comprehensive picture of the temporal patterns of gene expression leading to different fates of radial glial progenitors during neocortex layer formation.