title: Tau's role in the developing brain: implications for intellectual disability.
abstract: Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sapir
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
authors.forename: Talia
authors.initials: T
authors.lastname: Levy
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: Orly
authors.initials: O
authors.lastname: Reiner
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D002478:Cells, Cultured; D003712:Dendrites / Q000648:ultrastructure; D018274:Electroporation; D004622:Embryo, Mammalian; D047108:Embryonic Development; D055785:Gene Knockdown Techniques; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000648:ultrastructure; D009457:Neuroglia / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000648:ultrastructure; D034741:RNA, Small Interfering; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C558298:Mapt protein, mouse; D034741:RNA, Small Interfering; D016875:tau Proteins