title: Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors.
abstract: 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.
authors.affiliation: CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, Fontenay-aux-Roses, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Sii-Felice
authors.forename: Olivier
authors.initials: O
authors.lastname: Etienne
authors.forename: Françoise
authors.initials: F
authors.lastname: Hoffschir
authors.forename: Céline
authors.initials: C
authors.lastname: Mathieu
authors.forename: Lydia
authors.initials: L
authors.lastname: Riou
authors.forename: Vilma
authors.initials: V
authors.lastname: Barroca
authors.forename: Céline
authors.initials: C
authors.lastname: Haton
authors.forename: Fré
authors.initials: F
authors.lastname: Arwert
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouchet
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Mouthon
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology* / Q000196:embryology; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D004260:DNA Repair; D047108:Embryonic Development; D005199:Fanconi Anemia; D052217:Fanconi Anemia Complementation Group A Protein / Q000172:deficiency* / Q000235:genetics; D052241:Fanconi Anemia Complementation Group G Protein / Q000172:deficiency* / Q000235:genetics; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology*
chemical_list: C120277:Fanca protein, mouse; C499910:Fancg protein, mouse; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein