Failed clearance of aneuploid embryonic neural progenitor cells leads to excess aneuploidy in the Atm-deficient but not the Trp53-deficient adult cerebral cortex

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Michael J McConnellC Barlow

Abstract

Aneuploid neurons populate the normal adult brain, but the cause and the consequence of chromosome abnormalities in the CNS are poorly defined. In the adult cerebral cortex of three genetic mutants, one of which is a mouse model of the human neurodegenerative disease ataxia-telangiectasia (A-T), we observed divergent levels of sex chromosome (XY) aneuploidy. Although both A-T mutated (Atm)- and transformation related protein 53 (Trp53)-dependent mechanisms are thought to clear newly postmitotic neurons with chromosome abnormalities, we found a 38% increase in the prevalence of XY aneuploidy in the adult Atm-/- cerebral cortex and a dramatic 78% decrease in Trp53-/- mutant mice. A similar 43% decrease in adult XY aneuploidy was observed in DNA repair-deficient Xrcc5-/- mutants. Additional investigation found an elevated incidence of aneuploid embryonic neural progenitor cells (NPCs) in all three mutants, but elevated apoptosis, a likely fate of embryonic NPCs with severe chromosome abnormalities, was observed only in Xrcc5-/- mutants. These data lend increasing support to the hypothesis that hereditary mutations such as ATM-deficiency, which render abnormal cells resistant to developmental clearance, can lead to late-manifesting...Continue Reading

Citations

Oct 6, 2007·Immunologic Research·Richard A GattiRobert A Good
Apr 25, 2012·Molecular Neurobiology·Thomas Arendt
May 6, 2005·Nature Medicine·Carrolee Barlow, Kai Treuner
Apr 12, 2005·Nature Medicine·Pierre-Olivier FrappartZhao-Qi Wang
Nov 16, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suzanne E PetersonJerold Chun
May 27, 2009·International Journal of Molecular Sciences·Thomas ArendtMarkus Morawski
Apr 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·M A KingsburyJ Chun
Oct 13, 2012·Annual Review of Cell and Developmental Biology·Charles A ThomasAlysson R Muotri
Feb 4, 2010·The Journal of Cell Biology·Sarah L Thompson, Duane A Compton
Nov 18, 2005·The Journal of Cell Biology·Sylvian Bauer, Paul H Patterson
Aug 26, 2010·The Journal of Comparative Neurology·Jurjen W WestraJerold Chun
Oct 16, 2015·Nature Reviews. Neuroscience·Hei-man Chow, Karl Herrup
May 27, 2005·Current Opinion in Genetics & Development·Barbara F Hales
May 28, 2013·Mechanisms of Ageing and Development·Karl Herrup
May 18, 2010·Trends in Neurosciences·Tatjana SingerFred H Gage
Dec 27, 2006·Cancer Cell·Beth A A WeaverDon W Cleveland
Sep 25, 2007·Cell·Ulrich RassStephen C West
Aug 23, 2011·PloS One·Suzanne E PetersonJerold Chun
Dec 2, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·M O ObiakorC D Ezeonyejiaku
Mar 8, 2013·Seminars in Cell & Developmental Biology·Diane M Bushman, Jerold Chun
May 19, 2009·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·A M FernandesS K Rehen
Jul 22, 2018·Developmental Neurobiology·Suzanne RohrbackJerold Chun
May 8, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Nadine MichelMichael J McConnell
Apr 30, 2017·Science·Michael J McConnellUNKNOWN Brain Somatic Mosaicism Network
Apr 22, 2018·Molecular Psychiatry·Tomohisa TodaFred H Gage
Sep 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Suzanne RohrbackJerold Chun
May 22, 2019·Genes·Ivan Y IourovSergei I Kutsev
Apr 25, 2017·Journal of Alzheimer's Disease : JAD·Edward FielderDiana Jurk
Dec 4, 2019·Frontiers in Genetics·Huntington PotterAntoneta Granic
Jan 24, 2019·Cell Reports·William D ChronisterMichael J McConnell
Dec 12, 2017·Current Opinion in Systems Biology·Apuã C M PaquolaFred H Gage

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