Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish

  1. Sol Pose-Méndez  Is a corresponding author
  2. Paul Schramm
  3. Barbara Winter
  4. Jochen C Meier
  5. Konstantinos Ampatzis
  6. Reinhard W Köster  Is a corresponding author
  1. Technische Universität Braunschweig, Germany
  2. Karolinska Institute, Sweden

Abstract

Zebrafish have an impressive capacity to regenerate neurons in the central nervous system. However, regeneration of the principal neuron of the evolutionary conserved cerebellum, the Purkinje cell (PC), is believed to be limited to developmental stages based on invasive lesions. In contrast, non-invasive cell type specific ablation by induced apoptosis closely represents a process of neurodegeneration. We demonstrate that the ablated larval PC population entirely recovers in number, quickly reestablishes electrophysiological properties, and properly integrates into circuits to regulate cerebellum-controlled behavior. PC progenitors are present in larvae and adults, and PC ablation in adult cerebelli results in an impressive PC regeneration of different PC subtypes able to restore behavioral impairments. Interestingly, caudal PCs are more resistant to ablation and regenerate more efficiently, suggesting a rostro-caudal pattern of de- and regeneration properties. These findings demonstrate that the zebrafish cerebellum is able to regenerate functional PCs during all stages of the animal's life.

Data availability

Detailed numbers for statistics shown in the figures are provided in Supplementary Table 1. All data generated or analyzed during this study are included in the manuscript and supporting files.Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact.

Article and author information

Author details

  1. Sol Pose-Méndez

    Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    For correspondence
    s.pose-mendez@tu-braunschweig.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Paul Schramm

    Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0894-2348
  3. Barbara Winter

    Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jochen C Meier

    Cell Physiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Konstantinos Ampatzis

    Neuroscience Department, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7998-6463
  6. Reinhard W Köster

    Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    For correspondence
    r.koester@tu-bs.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6593-8196

Funding

Horizon 2020 Framework Programme (H2020-MSCA-IF-2015,No 703961)

  • Sol Pose-Méndez

Volkswagen Foundation (HOMEO-HIRN,ZN3673)

  • Jochen C Meier
  • Reinhard W Köster

Bundesministerium für Bildung und Forschung (Era-Net NEURON II CIPRESS)

  • Jochen C Meier

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

Reviewing Editor

  1. Paola Bovolenta, CSIC-UAM, Spain

Ethics

Animal experimentation: All experimental protocols for animal research were approved by governmental authorities of Lower Saxony, LAVES, (AZ33.19-42502-04-20/3593). All efforts were made to use only the minimum number of experimental animals necessary to obtain reliable scientific data.

Version history

  1. Received: April 22, 2022
  2. Preprint posted: May 10, 2022 (view preprint)
  3. Accepted: April 11, 2023
  4. Accepted Manuscript published: April 12, 2023 (version 1)
  5. Version of Record published: April 28, 2023 (version 2)

Copyright

© 2023, Pose-Méndez 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. Sol Pose-Méndez
  2. Paul Schramm
  3. Barbara Winter
  4. Jochen C Meier
  5. Konstantinos Ampatzis
  6. Reinhard W Köster
(2023)
Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish
eLife 12:e79672.
https://doi.org/10.7554/eLife.79672

Share this article

https://doi.org/10.7554/eLife.79672

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