1. Cell Biology
  2. Developmental Biology

Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development

  1. Ricardo Viais
  2. Marcos Fariña-Mosquera
  3. Marina Villamor-Payà
  4. Sadanori Watanabe
  5. Lluís Palenzuela
  6. Cristina Lacasa
  7. Jens Lüders  Is a corresponding author
  1. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Spain
  2. Division of Biological Science, Graduate School of Science, Nagoya University, Japan
https://doi.org/10.7554/eLife.67989
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  1. Ricardo Viais
  2. Marcos Fariña-Mosquera
  3. Marina Villamor-Payà
  4. Sadanori Watanabe
  5. Lluís Palenzuela
  6. Cristina Lacasa
  7. Jens Lüders
(2021)
Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development
eLife 10:e67989.
https://doi.org/10.7554/eLife.67989
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Abstract

Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and abortion of brain development. Co-deletion of Trp53 rescued cell death, but surviving progenitors failed to organize a pseudostratified epithelium, and brain development still failed. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Thus, in contrast to centrosomes, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.

Data availability

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

Article and author information

Author details

  1. Ricardo Viais

    Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    Competing interests
    No competing interests declared.

  2. Marcos Fariña-Mosquera

    Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    Competing interests
    No competing interests declared.

  3. Marina Villamor-Payà

    Cancer Science, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7288-4197

  4. Sadanori Watanabe

    Division of Biological Science, Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
    Competing interests
    No competing interests declared.

  5. Lluís Palenzuela

    Cancer Science, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0295-5225

  6. Cristina Lacasa

    Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    Competing interests
    No competing interests declared.

  7. Jens Lüders

    Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
    For correspondence
    jens.luders@irbbarcelona.org
    Competing interests
    Jens Lüders, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9018-7977

Funding

Ministerio de Economía, Industria y Competitividad, Gobierno de España (BFU2015-69275-P)

  • Jens Lüders

Ministerio de Ciencia, Innovación y Universidades (PGC2018-099562-B-I00)

  • Jens Lüders

Agència de Gestió d'Ajuts Universitaris i de Recerca (2017 SGR 1089)

  • Jens Lüders

Ministerio de Ciencia, Innovación y Universidades (SVP-2014-068770)

  • Ricardo Viais

Japan Society for the Promotion of Science (15H06270)

  • Sadanori Watanabe

Ministerio de Ciencia, Innovación y Universidades (PRE2019-089526)

  • Marcos Fariña-Mosquera

Ministerio de Ciencia, Innovación y Universidades (RED2018-102723-T)

  • Jens Lüders

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States

Ethics

Animal experimentation: All the mouse strains were maintained on a mixed 129/SvEv-C57BL/6 background in strict accordance with the European Community (2010/63/UE) guidelines in the Specific-Pathogen Free (SPF) animal facilities of the Barcelona Science Park (PCB). All protocols were approved by the Animal Care and Use Committee of the PCB/University of Barcelona (IACUC; CEEA-PCB) and by the Departament de Territori I Sostenibilitat of the Generalitat de Catalunya in accordance with applicable legislation (Real Decreto 53/2013). All efforts were made to minimize use and suffering.

Version history

  1. Preprint posted: November 18, 2020 (view preprint)
  2. Received: March 2, 2021
  3. Accepted: August 16, 2021
  4. Accepted Manuscript published: August 24, 2021 (version 1)
  5. Version of Record published: August 31, 2021 (version 2)

Copyright

© 2021, Viais 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. Ricardo Viais
  2. Marcos Fariña-Mosquera
  3. Marina Villamor-Payà
  4. Sadanori Watanabe
  5. Lluís Palenzuela
  6. Cristina Lacasa
  7. Jens Lüders
(2021)
Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development
eLife 10:e67989.
https://doi.org/10.7554/eLife.67989

Share this article

https://doi.org/10.7554/eLife.67989

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