C3G/Rapgef1 Is Required in Multipolar Neurons for the Transition to a Bipolar Morphology during Cortical Development.
The establishment of a polarized morphology is essential for the development and function of neurons. During the development of the mammalian neocortex, neurons arise in the ventricular zone (VZ) from radial glia cells (RGCs) and leave the VZ to generate the cortical plate (CP). During their migration, newborn neurons first assume a multipolar morphology in the subventricular zone (SVZ) and lower intermediate zone (IZ). Subsequently, they undergo a multi-to-bipolar (MTB) transition to become bipolar in the upper IZ by developing a leading process and a trailing axon. The small GTPases Rap1A and Rap1B act as master regulators of neural cell polarity in the developing mouse neocortex. They are required for maintaining the polarity of RGCs and directing the MTB transition of multipolar neurons. Here we show that the Rap1 guanine nucleotide exchange factor (GEF) C3G (encoded by the Rapgef1 gene) is a crucial regulator of the MTB transition in vivo by conditionally inactivating the Rapgef1 gene in the developing mouse cortex at different time points during neuronal development. Inactivation of C3G results in defects in neuronal migration, axon formation and cortical lamination. Live cell imaging shows that C3G is required in cortical neurons for both the specification of an axon and the initiation of radial migration by forming a leading process.
Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
Bhavin
B
Shah
Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany.
Daniela
D
Lutter
Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
Magdalena L
ML
Bochenek
Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
Katsuhiro
K
Kato
Institute of Medical Physics and Biophysics, Robert-Koch Straße 31, D-48149 Münster, Germany.
Yaroslav
Y
Tsytsyura
Institute of Medical Physics and Biophysics, Robert-Koch Straße 31, D-48149 Münster, Germany.
Natalia
N
Glyvuk
College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.
Akira
A
Sakakibara
Institute of Medical Physics and Biophysics, Robert-Koch Straße 31, D-48149 Münster, Germany.
Jürgen
J
Klingauf
Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
Ralf H
RH
Adams
Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
Andreas W
AW
Püschel
D000818:Animals; D016764:Cell Polarity; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D020668:rap GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D020735:Guanine Nucleotide-Releasing Factor 2; C492136:Rap1b protein, mouse; D020668:rap GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins