Dentate gyrus development requires a cortical hem-derived astrocytic scaffold

During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.

Automated summary

During embryonic development, timely regulation of the switch between radial glial cells, neurons, and astrocytes is crucial for coordinated interactions in the brain. The deletion of the SOX9 gene in early mouse brain development resulted in compromised dentate gyrus development, highlighting the importance of SOX9 in regulating astroglial potential acquisition in the cortical hem. This study demonstrates the formation of a local network between astrocytic and neuronal progenitors from adjacent domains, essential for brain morphogenesis.