PUBLICATION
RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum
- Authors
- Nobilleau, F., Audet, S., da Silva Babinet, A., Tork, S., Zaouter, C., Liao, M., Pilon, N., Tétreault, M., Patten, S.A., Samarut, É.
- ID
- ZDB-PUB-250702-18
- Date
- 2025
- Source
- Nature communications 16: 60196019 (Journal)
- Registered Authors
- Samarut, Eric
- Keywords
- none
- MeSH Terms
-
- Purkinje Cells/metabolism
- Neurogenesis/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Gene Expression Regulation, Developmental
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Neural Stem Cells*/cytology
- Neural Stem Cells*/metabolism
- Animals
- Replication Protein C*/genetics
- Replication Protein C*/metabolism
- Cerebellum*/cytology
- Cerebellum*/embryology
- Cerebellum*/growth & development
- Cerebellum*/metabolism
- PubMed
- 40595562 Full text @ Nat. Commun.
Citation
Nobilleau, F., Audet, S., da Silva Babinet, A., Tork, S., Zaouter, C., Liao, M., Pilon, N., Tétreault, M., Patten, S.A., Samarut, É. (2025) RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum. Nature communications. 16:60196019.
Abstract
DNA replication and repair are basic yet essential molecular processes for all cells. RFC1 encodes the largest subunit of the Replication Factor C, an essential clamp-loader for DNA replication and repair. Intronic repeat expansion in RFC1 has recently been associated with so-called RFC1-related disorders, which mainly encompass late-onset cerebellar ataxias. However, the mechanisms making certain tissues more susceptible to defects in these universal pathways remain mysterious. Here, we provide the first investigation of RFC1 gene function in vivo using zebrafish. We showed that RFC1 is expressed in neural progenitor cells within the developing cerebellum, where it maintains their genomic integrity during neurogenic maturation. Accordingly, RFC1 loss-of-function leads to a severe cerebellar phenotype due to impaired neurogenesis of both Purkinje and granule cells. Our data point to a specific role of RFC1 in the developing cerebellum, paving the way for a better understanding of the pathogenic mechanisms underlying RFC1-related disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping