Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells.
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.
Toyofuku
Toshihiko
T
Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Yoshida
Junko
J
Sugimoto
Tamiko
T
Yamamoto
Midori
M
Makino
Nobuhiko
N
Takamatsu
Hyota
H
Takegahara
Noriko
N
Suto
Fumikazu
F
Hori
Masatsugu
M
Fujisawa
Hajime
H
Kumanogoh
Atsushi
A
Kikutani
Hitoshi
H
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*
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