title: Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.
abstract: A hallmark of neurogenesis in the vertebrate brain is the apical-basal nuclear oscillation in polarized neural progenitor cells. Known as interkinetic nuclear migration (INM), these movements are synchronized with the cell cycle such that nuclei move basally during G1-phase and apically during G2-phase. However, it is unknown how the direction of movement and the cell cycle are tightly coupled. Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms. During S to G2 progression, the microtubule-associated protein Tpx2 redistributes from the nucleus to the apical process, and promotes nuclear migration during G2-phase by altering microtubule organization. Thus, Tpx2 links cell-cycle progression and autonomous apical nuclear migration. In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically. Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.
authors: Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Japan. kosodo@med.kawasaki-m.ac.jp
authors: Yoichi
authors: Y
authors: Kosodo
authors: Taeko
authors: T
authors: Suetsugu
authors: Masumi
authors: M
authors: Suda
authors: Yuko
authors: Y
authors: Mimori-Kiyosue
authors: Kazunori
authors: K
authors: Toida
authors: Shoji A
authors: SA
authors: Baba
authors: Akatsuki
authors: A
authors: Kimura
authors: Fumio
authors: F
authors: Matsuzaki
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D051379:Mice; D008856:Microscopy, Fluorescence; D008863:Microspheres; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology*; D008958:Models, Molecular; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D059008:Time-Lapse Imaging
chemical_list: D017931:DNA Primers; D008869:Microtubule-Associated Proteins