ABSTRACT
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 towards 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Fig. 1 and S.1 updated with behavioural analysis of adult Sox9 mutants compared to controls. Fig. 2 and S.4 updated to analyse total number, proliferation and migration of early PAX6+ DG progenitors. Fig. 4 updated with 3D reconstruction to analyse progenitors and scaffold interaction. Supplemental videos available. Fig. 5 updated to analyse the astrocytic nature of ALDH1L1+ cell in the CH. Fig. 6 and Fig. S. 10 updated with lineage tracing of CH-derived cells.