Multiple parallel cell lineages in the developing mammalian cerebral cortex.

Area of Science:

• Developmental Neuroscience
• Comparative Genomics
• Cell Biology

Background:

• The traditional view of cortical neurogenesis involves a simple linear progression from radial glia cells (RGCs) to basal progenitors and finally to neurons.
• The mechanisms governing neurogenesis in species with complex, folded cortices, such as humans, remain poorly understood.
• Understanding progenitor cell diversity and lineage progression is crucial for deciphering brain development and evolution.

Purpose of the Study:

• To investigate the molecular diversity and lineage relationships of progenitor cells in the developing mammalian cortex.
• To compare neurogenesis mechanisms in species with simple versus complex cortical structures, including humans.
• To identify conserved and divergent features of cortical development across mammalian evolution.

Main Methods:

• Employed single-cell RNA sequencing on individual cortical germinal zones from ferrets.
• Utilized barcoded lineage tracing to track progenitor cell fates and neuronal output.
• Integrated transcriptomic data with lineage information to define progenitor classes and their developmental trajectories.

Main Results:

• Identified multiple distinct classes of apical radial glia cells (RGCs) initiating parallel developmental lineages.
• Demonstrated that these parallel lineages converge onto a common class of newly generated neurons.
• Found that these parallel RGC classes and transcriptomic trajectories are conserved in ferret and human cortices but absent in mice, suggesting evolutionary adaptation in folded brains.

Conclusions:

• Cortical development in folded mammalian brains involves a multiplicity of progenitor cell lineages, not a simple linear progression.
• The observed parallel lineage patterns are conserved in humans and ferrets, highlighting their importance in complex cortical structures.
• Differential gene expression in neurons within gyri and sulci may relate to human cortical malformation genes, indicating functional specialization.