title: Rap1 GTPases Are Master Regulators of Neural Cell Polarity in the Developing Neocortex.
abstract: During the development of the mammalian neocortex, the generation of neurons by neural progenitors and their migration to the final position are closely coordinated. The highly polarized radial glial cells (RGCs) serve both as progenitor cells to generate neurons and as support for the migration of these neurons. After their generation, neurons transiently assume a multipolar morphology before they polarize and begin their migration along the RGCs. Here, we show that Rap1 GTPases perform essential functions for cortical organization as master regulators of cell polarity. Conditional deletion of Rap1 GTPases leads to a complete loss of cortical lamination. In RGCs, Rap1 GTPases are required to maintain their polarized organization. In newborn neurons, the loss of Rap1 GTPases prevents the formation of axons and leading processes and thereby interferes with radial migration. Taken together, the loss of RGC and neuronal polarity results in the disruption of cortical organization.
authors.affiliation: Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
authors.forename: Bhavin
authors.initials: B
authors.lastname: Shah
authors.affiliation: Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lutter
authors.affiliation: Institute of Medical Physics and Biophysics, D-48149 Münster, Germany.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsytsyura
authors.affiliation: Institute of Medical Physics and Biophysics, D-48149 Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Glyvuk
authors.affiliation: College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.|Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sakakibara
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.|Institute of Medical Physics and Biophysics, D- 48149 Münster, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klingauf
authors.affiliation: Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Püschel
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D063928:Ependymoglial Cells / Q000502:physiology; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C000620839:Rap1 protein, mouse; D020827:rap1 GTP-Binding Proteins
keywords: adherens junctions; axon formation; neuronal migration; neuronal polarity; radial glia