title: WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.
abstract: Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.
authors.affiliation: Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Min-Jue
authors.initials: MJ
authors.lastname: Xie
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuroda
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wang
authors.forename: Munekazu
authors.initials: M
authors.lastname: Komada
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Akira
authors.initials: A
authors.lastname: Sakakibara
authors.forename: Takaki
authors.initials: T
authors.lastname: Miyata
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nagata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Tokuichi
authors.initials: T
authors.lastname: Iguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sato
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D016264:Dextran Sulfate / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011247:Pregnancy; D034622:RNA Interference / Q000502:physiology; D014162:Transfection; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D016264:Dextran Sulfate; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C490756:Abi2 protein, mouse; C502089:Nckap1 protein, mouse; C492303:Wasf2 protein, mouse; C115472:Cyfip1 protein, mouse