title: Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells.
abstract: The cardiac neural crest, a subpopulation of the neural crest, contributes to the cardiac outflow tract formation during development. However, how it follows the defined long-range migratory pathway remains unclear. We show here that the migrating cardiac neural crest cells (NCCs) express Plexin-A2, Plexin-D1 and Neuropilin. The membrane-bound ligands for Plexin-A2, Semaphorin (Sema)6A and Sema6B, are expressed in the dorsal neural tube and the lateral pharyngeal arch mesenchyme (the NCC "routes"). Sema3C, a ligand for Plexin-D1/neuropilin-1, is expressed in the cardiac outflow tract (the NCC "target"). Sema6A and Sema6B repel neural crest cells, while Sema3C attracts neural crest cells. Sema6A and Sema6B repulsion and Sema3C attraction are diminished either when Plexin-A2 and Neuropilin-1, or when Plexin-D1, respectively, are knocked down in NCCs. When RNAi knockdown diminishes each receptor in NCCs, the NCCs fail to migrate into the cardiac outflow tract in the developing chick embryo. Furthermore, Plexin-A2-deficient mice exhibit defects of cardiac outflow tract formation. We therefore conclude that the coordination of repulsive cues provided by Sema6A/Sema6B through Plexin-A2 paired with the attractive cue by Sema3C through Plexin-D1 is required for the precise navigation of migrating cardiac NCCs.
authors.affiliation: Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toyofuku
authors.forename: Junko
authors.initials: J
authors.lastname: Yoshida
authors.forename: Tamiko
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Midori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Makino
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Suto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D006321:Heart / Q000196:embryology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D039921:Neuropilins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D039921:Neuropilins; C492113:Plxna2 protein, mouse; C473552:Plxnd1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins