Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish
- Technische Universität Braunschweig, Germany
- 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
Konstantinos Ampatzis
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.
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.
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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Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish
eLife 12:e79672.
https://doi.org/10.7554/eLife.79672
Further reading
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During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
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