Dentate gyrus development requires a cortical hem-derived astrocytic scaffold
Alessia Caramello1, Christophe Galichet1, Karine Rizzoti1
1Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, United Kingdom.
Elife
|January 4, 2021
Summary
SOX9 is crucial for mouse dentate gyrus development. Its deletion disrupts glial scaffold formation, impacting neuronal progenitor migration and brain morphogenesis.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Radial glial cells differentiate into neurons and then astrocytes via a gliogenic switch.
- Transcription factors regulate the gliogenic switch, essential for neuron-glia interactions.
- SOX9 is a key transcription factor involved in brain development.
Purpose of the Study:
- To investigate the role of SOX9 in embryonic mouse brain development, specifically the dentate gyrus (DG).
- To determine the cellular origin of SOX9-dependent defects in DG formation.
- To identify novel progenitor populations and their contribution to brain morphogenesis.
Main Methods:
- Embryonic deletion of the SOX9 gene in specific mouse brain progenitor domains.
- Analysis of dentate gyrus development and cellular composition.
- Identification and characterization of ALDH1L1+ astrocytic progenitors.
Main Results:
- Embryonic deletion of SOX9 severely impaired dentate gyrus development.
- Targeted deletion in the cortical hem (CH) revealed SOX9's role in ALDH1L1+ astrocytic progenitor formation.
- These progenitors create a glial scaffold vital for DG neuronal progenitor migration.
Conclusions:
- SOX9 plays an early, critical role in DG development by regulating astrocytic progenitor differentiation in the CH.
- Formation of local networks between adjacent astrocytic and neuronal progenitors is fundamental for brain morphogenesis.
- Uncharacterized astrocytic progenitors in the CH are essential for DG development.
