XLF/Cernunnos loss impairs mouse brain development by altering symmetric proliferative divisions of neural progenitors

• DOI: 10.1016/j.celrep.2023.112342
• Publication Date: 2023-04-06T05:00:16Z
• Authors: Amandine Bery; Olivier Etienne; Laura Mouton; Sofiane Mokrani; Christine Granoti...; Laurent R. Gauthier; Justyne Feat-Vetel; Thierry Kortulewski; Elodie A. Pérès; Chantal Desmaze; Philippe Lestaveal; Vilma Barroca; Antony Laugeray; Fawzi Boumezbeur; Vincent Abramovski; Stéphane Mortaud; Arnaud Menuet; Denis Le Bihan; Jean-Pierre de Vi...; François D. Boussin
• Keywords: Microcephaly; Neural Development; Progenitor

XLF/Cernunnos is a component of the ligation complex used in classical non-homologous end-joining (cNHEJ), major DNA double-strand break (DSB) repair pathway. We report neurodevelopmental delays and significant behavioral alterations associated with microcephaly Xlf-/- mice. This phenotype, reminiscent clinical neuropathologic features humans deficient cNHEJ, low level apoptosis neural cells premature neurogenesis, which consists an early shift progenitors from proliferative to neurogenic divisions during brain development. show that neurogenesis related increase chromatid breaks affecting mitotic spindle orientation, highlighting direct link between asymmetric chromosome segregation divisions. study reveals thus XLF required for maintaining symmetric development shows may play role pathologies caused by NHEJ deficiency and/or genotoxic stress.