title: Time-Specific Effects of Spindle Positioning on Embryonic Progenitor Pool Composition and Adult Neural Stem Cell Seeding.
abstract: The developmental mechanisms regulating the number of adult neural stem cells (aNSCs) are largely unknown. Here we show that the cleavage plane orientation in murine embryonic radial glia cells (RGCs) regulates the number of aNSCs in the lateral ganglionic eminence (LGE). Randomizing spindle orientation in RGCs by overexpression of Insc or a dominant-negative form of Lgn (dnLgn) reduces the frequency of self-renewing asymmetric divisions while favoring symmetric divisions generating two SNPs. Importantly, these changes during embryonic development result in reduced seeding of aNSCs. Interestingly, no effects on aNSC numbers were observed when Insc was overexpressed in postnatal RGCs or aNSCs. These data suggest a new mechanism for controlling aNSC numbers and show that the role of spindle orientation during brain development is highly time and region dependent.
authors.affiliation: Institute for Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Physiological Genomics, Biomedical Center, Ludwig-Maximilian University Munich, 82152 Planegg/Munich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Falk
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, IBDM, UMR7288, 13284 Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bugeon
authors.affiliation: Institute for Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Physiological Genomics, Biomedical Center, Ludwig-Maximilian University Munich, 82152 Planegg/Munich, Germany.
authors.forename: Jovica
authors.initials: J
authors.lastname: Ninkovic
authors.affiliation: Institute for Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Gregor-Alexander
authors.initials: GA
authors.lastname: Pilz
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), 1030 Vienna, Austria.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Postiglione
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, IBDM, UMR7288, 13284 Marseille, France.
authors.forename: Harold
authors.initials: H
authors.lastname: Cremer
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), 1030 Vienna, Austria.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Knoblich
authors.affiliation: Institute for Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Physiological Genomics, Biomedical Center, Ludwig-Maximilian University Munich, 82152 Planegg/Munich, Germany; SYNERGY, Excellence Cluster of Systems Neurology, Biomedical Center, Ludwig-Maximilian University Munich, 82152 Planegg/Munich, Germany. Electronic address: magdalena.goetz@helmholtz-muenchen.de.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology*; D008941:Spindle Apparatus
keywords: Insc; Lgn; SEZ; adult neural stem cells; division plane; radial glial cells; short neural precursor