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

Author

Listed:
  • Fanny Nobilleau

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM))

  • Sébastien Audet

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM))

  • Alexandra da Silva Babinet

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM))

  • Sanaa Tork

    (Université du Québec à Montréal (UQAM)
    Université du Québec à Montréal)

  • Charlotte Zaouter

    (INRS- Centre Armand-Frappier Santé Biotechnologie)

  • Meijiang Liao

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM))

  • Nicolas Pilon

    (Université du Québec à Montréal (UQAM)
    Université du Québec à Montréal
    Université de Montréal)

  • Martine Tétreault

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM)
    Université du Québec à Montréal)

  • Shunmoogum A. Patten

    (Université de Montréal
    Université du Québec à Montréal
    INRS- Centre Armand-Frappier Santé Biotechnologie)

  • Éric Samarut

    (Université de Montréal
    University of Montréal Hospital Research Center (CRCHUM)
    Université du Québec à Montréal)

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.

Suggested Citation

  • Fanny Nobilleau & Sébastien Audet & Alexandra da Silva Babinet & Sanaa Tork & Charlotte Zaouter & Meijiang Liao & Nicolas Pilon & Martine Tétreault & Shunmoogum A. Patten & Éric Samarut, 2025. "RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60775-5
    DOI: 10.1038/s41467-025-60775-5
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