title: The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex.
abstract: In the developing neocortex, progenitor cells expand through symmetric division before they generate cortical neurons through multiple rounds of asymmetric cell division. Here, we show that the orientation of the mitotic spindle plays a crucial role in regulating the transition between those two division modes. We demonstrate that the protein phosphatase PP4c regulates spindle orientation in early cortical progenitor cells. Upon removing PP4c, mitotic spindles fail to orient in parallel to the neuroepithelial surface and progenitors divide with random orientation. As a result, their divisions become asymmetric and neurogenesis starts prematurely. Biochemical and genetic experiments show that PP4c acts by dephosphorylating the microtubule binding protein Ndel1, thereby enabling complex formation with Lis1 to form a functional spindle orientation complex. Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr-Gasse 3-5, 1030 Vienna, Austria.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Xie
authors.forename: Christoph
authors.initials: C
authors.lastname: Jüschke
authors.forename: Christopher
authors.initials: C
authors.lastname: Esk
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology; D055495:Neurogenesis / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D011247:Pregnancy; D008941:Spindle Apparatus / Q000201:enzymology*
chemical_list: D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4