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  • The EMBO Journal (2008) 27, 770 - 781
  • doi:10.1038/emboj.2008.14

Published online: 31 January 2008

Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors

Karine Sii-Felice1, Olivier Etienne1, Françoise Hoffschir1, Céline Mathieu1, Lydia Riou2, Vilma Barroca2, Céline Haton1, Fré Arwert3, Pierre Fouchet2, François D Boussin1 and Marc-André Mouthon1

  1. CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, Fontenay-aux-Roses, France
  2. CEA, DSV, iRCM, SCSR, Laboratoire de Gametogenèse, Apoptose et Genotoxicité, INSERM U566-Université Paris 7, Fontenay-aux-Roses, France
  3. Department of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands

Correspondence to:

Marc-André Mouthon, CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, BP n°6, Fontenay-aux-Roses Cedex 92265, France. Tel.: +33 146 549 461; Fax: +33 146 549 180; E-mail: marc-andre.mouthon@cea.fr

Received 9 August 2007; Accepted 11 January 2008

Although brain development abnormalities and brain cancer predisposition have been reported in some Fanconi patients, the possible role of Fanconi DNA repair pathway during neurogenesis is unclear. We thus addressed the role of fanca and fancg, which are involved in the activation of Fanconi pathway, in neural stem and progenitor cells during brain development and adult neurogenesis. Fanca -/- and fancg -/- mice presented with microcephalies and a decreased neuronal production in developing cortex and adult brain. Apoptosis of embryonic neural progenitors, but not that of postmitotic neurons, was increased in the neocortex of fanca -/- and fancg -/- mice and was correlated with chromosomal instability. In adult Fanconi mice, we showed a reduced proliferation of neural progenitor cells related to apoptosis and accentuated neural stem cells exhaustion with ageing. In addition, embryonic and adult Fanconi neural stem cells showed a reduced capacity to self-renew in vitro. Our study demonstrates a critical role for Fanconi pathway in neural stem and progenitor cells during developmental and adult neurogenesis.

  • Keywords:

    • ageing,
    • apotosis,
    • DNA repair,
    • Fanconi,
    • neural progenitor