Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex

  1. Ayse Güven
  2. Nereo Kalebic
  3. Katherine R Long
  4. Marta Florio
  5. Samir Vaid
  6. Holger Brandl
  7. Denise Stenzel
  8. Wieland B Huttner  Is a corresponding author
  1. 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

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Ayse Güven

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Nereo Kalebic

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8445-2906
  3. Katherine R Long

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0660-2486
  4. Marta Florio

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Samir Vaid

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Holger Brandl

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1911-8570
  7. Denise Stenzel

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Wieland B Huttner

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    huttner@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4143-7201

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.

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).

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Version history

  1. Received: June 30, 2019
  2. Accepted: March 18, 2020
  3. Accepted Manuscript published: March 19, 2020 (version 1)
  4. 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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  1. Ayse Güven
  2. Nereo Kalebic
  3. Katherine R Long
  4. Marta Florio
  5. Samir Vaid
  6. Holger Brandl
  7. Denise Stenzel
  8. Wieland B Huttner
(2020)
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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