biostudies-literature00450Caramello ACancer Research UKMedical Research CouncilThe Francis Crick InstituteWellcome TrustNIH HHSe63904https://www.ebi.ac.uk/biostudies/studies/S-EPMC7806271biostudies-literatureUnknown10During 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 <i>Sox9</i> 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.eLifeDentate gyrus development requires a cortical hem-derived astrocytic scaffold.PMC780627110107FC001107U117562207U117512772U117570590U42 OD010918Caramello ARizzoti KGalichet CLovell-Badge R45falseDentate 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 <i>Sox9</i> 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.2021-01-01T00:00:00Z2021 Jan2024-10-19T10:08:37.061Z2021-02-21T00:38:26ZS-EPMC78062713339390510.7554/eLife.63904