title: Pioneering axons regulate neuronal polarization in the developing cerebral cortex.
abstract: The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Namba
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kibe
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Funahashi
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakamuta
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takano
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Kozawa
authors.affiliation: Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Experimental Animal Resource, Brain Research Institute, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata, Niigata 951-8510, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Oda
authors.affiliation: Division of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata, Niigata 951-8510, Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Department of Neurobiology, University of Tsukuba School of Medicine, Ibaraki 305-8577, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sakakibara
authors.affiliation: Division of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata, Niigata 951-8510, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286 CNRS, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Faivre-Sarrailh
authors.affiliation: Division of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata, Niigata 951-8510, Japan; Department of Biology, School of Medicine, Aichi Medical University, Yazako, Nagakute, Aichi 480-1195, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan. Electronic address: kaibuchi@med.nagoya-u.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D058969:Contactin 2 / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein