title: In vivo knockdown of ErbB3 in mice inhibits Schwann cell precursor migration.
abstract: The myelin sheath insulates neuronal axons and markedly increases the nerve conduction velocity. In the peripheral nervous system (PNS), Schwann cell precursors migrate along embryonic neuronal axons to their final destinations, where they eventually wrap around individual axons to form the myelin sheath after birth. ErbB2 and ErbB3 tyrosine kinase receptors form a heterodimer and are extensively expressed in Schwann lineage cells. ErbB2/3 is thought to be one of the primary regulators controlling the entire Schwann cell development. ErbB3 is the bona fide Schwann cell receptor for the neuronal ligand neuregulin-1. Although ErbB2/3 is well known to regulate both Schwann cell precursor migration and myelination by Schwann cells in fishes, it still remains unclear whether in mammals, ErbB2/3 actually regulates Schwann cell precursor migration. Here, we show that knockdown of ErbB3 using a Schwann cell-specific promoter in mice causes delayed migration of Schwann cell precursors. In contrast, littermate control mice display normal migration. Similar results are seen in an in vitro migration assay using reaggregated Schwann cell precursors. Also, ErbB3 knockdown in mice reduces myelin thickness in sciatic nerves, consistent with the established role of ErbB3 in myelination. Thus, ErbB3 plays a key role in migration, as well as in myelination, in mouse Schwann lineage cells, presenting a genetically conservative role of ErbB3 in Schwann cell precursor migration.
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Torii
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.affiliation: Laboratory Animal Facility, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsumura
authors.affiliation: Laboratory Animal Facility, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Inashiki, Ibaraki 200-1192, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ohbuchi
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Inashiki, Ibaraki 200-1192, Japan; School of Medicine, Keio University, Shinjuku, Tokyo 160-8583, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan. Electronic address: yamauchi-j@ncchd.go.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamauchi
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction
chemical_list: D020890:Neuregulin-1; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C490581:Nrg1 protein, mouse; C524056:Erbb2 protein, mouse
keywords: ErbB3; In vivo knockdown; Migration; Mouse; Schwann cell precursor