title: Developmental Expression of 4-Repeat-Tau Induces Neuronal Aneuploidy in Drosophila Tauopathy Models.
abstract: Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. Interestingly, the relative expression levels of Tau isoforms containing either 3 (3R-Tau) or 4 repeats (4R-Tau) play an important role both during brain development and neurodegeneration. Here, we used genetic and cellular tools to study the link between 3R and 4R-Tau isoform expression, mitotic progression in neuronal progenitors and post-mitotic neuronal survival. Our results illustrated that the severity of Tau-induced adult phenotypes depends on 4R-Tau isoform expression during development. As recently described, we observed a mitotic delay in 4R-Tau expressing cells of larval eye discs and brains. Live imaging revealed that the spindle undergoes a cycle of collapse and recovery before proceeding to anaphase. Furthermore, we found a high level of aneuploidy in post-mitotic differentiated tissue. Finally, we showed that overexpression of wild type and mutant 4R-Tau isoform in neuroblastoma SH-SY5Y cell lines is sufficient to induce monopolar spindles. Taken together, our results suggested that neurodegeneration could be in part linked to neuronal aneuploidy caused by 4R-Tau expression during brain development.
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Malmanche
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dourlen
authors.affiliation: Laboratory of Behavioral and Developmental Genetics, Center for Human Genetics, KU Leuven, Leuven, 3000, Belgium.|VIB Center for the Biology of Disease, Leuven, 3000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Gistelinck
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Florie
authors.initials: F
authors.lastname: Demiautte
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Link
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Cloé
authors.initials: C
authors.lastname: Dupont
authors.affiliation: Laboratory of Behavioral and Developmental Genetics, Center for Human Genetics, KU Leuven, Leuven, 3000, Belgium.|VIB Center for the Biology of Disease, Leuven, 3000, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: Vanden Broeck
authors.affiliation: Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.|Center for Infection and Immunity of Lille, 59019, France.|Inserm UMR1019, Lille, 59019, France.|CNRS UMR8204, Lille, 59019, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Werkmeister
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.|Center for Infection and Immunity of Lille, 59019, France.|Inserm UMR1019, Lille, 59019, France.|CNRS UMR8204, Lille, 59019, France.
authors.forename: Antonino
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.|Center for Infection and Immunity of Lille, 59019, France.|Inserm UMR1019, Lille, 59019, France.|CNRS UMR8204, Lille, 59019, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bauderlique
authors.affiliation: Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Beerse, 2340, Belgium.
authors.forename: Dieder
authors.initials: D
authors.lastname: Moechars
authors.affiliation: CNRS UMR5095, Pessac, 33607, France.|Institut Européen de Chimie et Biologie, Pessac, 33607, France.|Institut de Biochimie et Génétique Cellulaires, Université de Bordeaux, Pessac, 33607, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Royou
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.|Howard Hughes Medical Institute, Houston, TX 77030, USA.|Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.|Jan and Dan Duncan Neurological Research Institute, Houston, TX 77030, USA.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
authors.affiliation: Center for Infection and Immunity of Lille, 59019, France.|Inserm UMR1019, Lille, 59019, France.|CNRS UMR8204, Lille, 59019, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Lafont
authors.affiliation: Laboratory of Behavioral and Developmental Genetics, Center for Human Genetics, KU Leuven, Leuven, 3000, Belgium.|VIB Center for the Biology of Disease, Leuven, 3000, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Callaerts
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.affiliation: Inserm UMR1167, Laboratoire d'Excellence Distalz, Lille, F59000, France.|Institut Pasteur de Lille, Longevity Research Center, Lille, F59000, France.|Université de Lille, Lille, F59000, France.|Center for Medical Genetics, Ghent University Hospital, Ghent University, Gent, 9000, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Dermaut
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D010786:Photoreceptor Cells / Q000378:metabolism; D020033:Protein Isoforms; D024801:Tauopathies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins