A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture

  1. Alfredo Llorca
  2. Gabriele Ciceri
  3. Robert Beattie
  4. Fong Kuan Wong
  5. Giovanni Diana
  6. Eleni Serafeimidou-Pouliou
  7. Marian Fernández-Otero
  8. Carmen Streicher
  9. Sebastian J Arnold
  10. Martin Meyer
  11. Simon Hippenmeyer
  12. Miguel Maravall
  13. Oscar Marin  Is a corresponding author
  1. King's College London, United Kingdom
  2. Institute of Science and Technology Austria, Austria
  3. University of Freiburg, Germany
  4. University of Sussex, United Kingdom

Abstract

The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Alfredo Llorca

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Gabriele Ciceri

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert Beattie

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Fong Kuan Wong

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Giovanni Diana

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7497-5271
  6. Eleni Serafeimidou-Pouliou

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Marian Fernández-Otero

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Carmen Streicher

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Sebastian J Arnold

    Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Martin Meyer

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Simon Hippenmeyer

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2279-1061
  12. Miguel Maravall

    Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8869-7206
  13. Oscar Marin

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    For correspondence
    oscar.marin@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6264-7027

Funding

H2020 European Research Council (ERC-2017-AdG 787355)

  • Oscar Marin

H2020 European Research Council (ERC-2016-CoG 725780)

  • Simon Hippenmeyer

European Molecular Biology Organization

  • Fong Kuan Wong

H2020 Marie Skłodowska-Curie Actions

  • Fong Kuan Wong

Austrian Science Fund (Lise-Meitner program M 2416)

  • Robert Beattie

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 procedures were approved by King's College London and IST Austria, and were performed under UK Home Office project licenses, and in accordance with Austrian Federal Ministry of Science and Research license, and European regulations (EU directive 86/609, EU decree 2001- 486).

Reviewing Editor

  1. Sonia Garel, Ecole Normale Superieure, France

Publication history

  1. Received: August 27, 2019
  2. Accepted: November 15, 2019
  3. Accepted Manuscript published: November 18, 2019 (version 1)
  4. Version of Record published: January 17, 2020 (version 2)

Copyright

© 2019, Llorca 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. Alfredo Llorca
  2. Gabriele Ciceri
  3. Robert Beattie
  4. Fong Kuan Wong
  5. Giovanni Diana
  6. Eleni Serafeimidou-Pouliou
  7. Marian Fernández-Otero
  8. Carmen Streicher
  9. Sebastian J Arnold
  10. Martin Meyer
  11. Simon Hippenmeyer
  12. Miguel Maravall
  13. Oscar Marin
(2019)
A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture
eLife 8:e51381.
https://doi.org/10.7554/eLife.51381
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