Multiple parallel cell lineages in the developing mammalian cerebral cortex

Abstract

Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.

Entosis implicates a new role for P53 in microcephaly pathogenesis, beyond apoptosis

“…These cells are abundant in the gyrated cortex but scarce in rodents. [12][13][14] Terminally differentiated neurons generated directly from aRGs or bRGs or indirectly from IPs depart the proliferative germinal layers and migrate to increase cortical thickness (Figure 1). [15,16] The pathogenesis of microcephaly is associated with reduced progenitor proliferation, premature progenitor differentiation, and compromised cortical cell survival which all result in reduced cortical cell numbers.…”