Dentate gyrus development requires a cortical hem-derived astrocytic scaffold
- The Francis Crick Institute, United Kingdom
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have moreover been provided where required.
Article and author information
Author details
Christophe Galichet
Funding
Medical Research Council (U117512772)
- Robin Lovell-Badge
Medical Research Council (U117562207)
- Robin Lovell-Badge
Medical Research Council (U117570590)
- Robin Lovell-Badge
Cancer Research UK (FC001107)
- Robin Lovell-Badge
Medical Research Council (FC001107)
- Robin Lovell-Badge
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments carried out on mice were approved under the UK Animal (scientificprocedures) Act 1986 (Project license n. 80/2405 and PP8826065).
Copyright
© 2021, Caramello et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dentate gyrus development requires a cortical hem-derived astrocytic scaffold
eLife 10:e63904.
https://doi.org/10.7554/eLife.63904
