Multiple parallel cell lineages in the developing mammalian cerebral cortex

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.This work was supported by ERC-AdG grant Neurocentro-885382 to M.G. and by Spanish State Research Agency grants SAF2015-69168-R, PGC2018-102172-B, and PDI2021-125618NB and “Severo Ochoa” Programme for Centers of Excellence in R&D (CEX-2021-00165-S) to V.B. Additional support was provided by Spanish State Research Agency FPI contract (BES-2016-077737) to L.D.-V.-A., “JdC incorporación” fellowship (IJC2020-044653-I) to V.F., and by Fundación Tatiana Pérez de Guzmán el Bueno fellowship to A.P.-C.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX-2021-00165-S).Peer reviewe