RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum

Nobilleau, Fanny; Audet, Sébastien; da Silva Babinet, Alexandra; Tork, Sanaa; Zaouter, Charlotte; Liao, Meijiang; Pilon, Nicolas; Tetreault, Martine; Patten, Shunmoogum A. ORCID: https://orcid.org/0000-0002-2782-3547 et Samarut, Eric (2025). RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum Nature Communications , vol. 16 , nº 6019. pp. 1-15. DOI: 10.1038/s41467-025-60775-5.

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Résumé

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.

Type de document:	Article
Informations complémentaires:	This work was funded by the Centre d’excellence en recherche sur les maladies orphelines—Fondation Courtois (CERMO-FC), by Génome Quebec and Ataxie Canada. E.S. and S.A.P. are supported by the Natural Science and Engineering Research Council (NSERC), Canadian Institutes of Health Research (CIHR), and are FRQS research scholars. M.T. is a Junior 2 FRQS research scholar. F.N. received M.Sc scholarships from CRCHUM and the Faculty of Medicine/Université de Montreal. S.A. received doctoral scholarships from CRCHUM, Faculty of Medicine/Université de Montreal, CERMO-FC, FRQS, and CIHR.
Mots-clés libres:	Neurogenesis, DNA replication, Neural stem cells
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	28 août 2025 18:36
Dernière modification:	28 août 2025 18:36
URI:	https://espace.inrs.ca/id/eprint/16579

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