Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.
During their migration, cerebellar granule cells switch from a tangential to a radial mode of migration. We have previously demonstrated that this involves the transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that controls Sema6A function in migrating granule cells. In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, as we saw in Sema6a mutants. A similar phenotype was observed in mutant mice that were generated by mutagenesis with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the semaphorin domain of plexin-A2. We found that this mutation abolished the ability of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using time-lapse video microscopy, we found that centrosome-nucleus coupling and coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-) granule cells. This suggests that semaphorin-plexin signaling modulates cell migration by controlling centrosome positioning.
Renaud
Julie
J
Centre National de la Recherche Scientifique, UMR7102, 9 Quai Saint-Bernard, Paris F-75005, France.
Kerjan
Géraldine
G
Sumita
Itsuko
I
Zagar
Yvrick
Y
Georget
Virginie
V
Kim
Doyeun
D
Fouquet
Coralie
C
Suda
Kazunori
K
Sanbo
Makoto
M
Suto
Fumikazu
F
Ackerman
Susan L
SL
Mitchell
Kevin J
KJ
Fujisawa
Hajime
H
Chédotal
Alain
A
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; C492113:Plxna2 protein, mouse; D011956:Receptors, Cell Surface; C504203:Sema6a protein, mouse; D039961:Semaphorins