Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex
- Max Planck Institute of Molecular Cell Biology and Genetics, Germany
Abstract
Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that the transcription factor Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. We show that Sox9 is expressed in human and ferret BPs and is required for BP proliferation in embryonic ferret neocortex. Conditional Sox9 expression in the mouse BP lineage, where it normally is not expressed, increases BP proliferation, reduces Tbr2 levels and induces Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell-non-autonomous stimulation of BP proliferation followed by increased upper-layer neuron production. Our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic vs. gliogenic BP cell fate, suggesting that Sox9 may have contributed to promote neocortical expansion.
Data availability
Sequencing data have been deposited in GEO under accession code GSE134162
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Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansionNCBI Gene Expression Omnibus, GSE65000.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SFB 655,A2)
- Wieland B Huttner
European Research Council (250197)
- Wieland B Huttner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marianne E Bronner, California Institute of Technology, United States
Ethics
Animal experimentation: All animal experiments in this study were conducted according to the German animal welfare legislation. All experiments utilizing mice and ferrets were conducted in agreement with the German Animal Welfare Legislation after approval by the Landesdirektion Sachsen (licence TVV 05/2015 and TVV 21/2017).
Human subjects: Human fetal neocortical tissue was provided by the Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Carl Gustav Carus, involving elective pregnancy terminations with informed written maternal consents and approval by the local University Hospital Ethical Committees. Human fetal neocortical tissue was also obtained from Novogenix Laboratories (Torrance, CA).
Version history
- Received: June 30, 2019
- Accepted: March 18, 2020
- Accepted Manuscript published: March 19, 2020 (version 1)
- Version of Record published: March 30, 2020 (version 2)
Copyright
© 2020, Güven 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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Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex
eLife 9:e49808.
https://doi.org/10.7554/eLife.49808
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