Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers.
Hippocampal mossy fibers project preferentially to the stratum lucidum, the proximal-most lamina of the suprapyramidal region of CA3. The molecular mechanisms that govern this lamina-restricted projection are still unknown. We examined the projection pattern of mossy fibers in mutant mice for semaphorin receptors plexin-A2 and plexin-A4, and their ligand, the transmembrane semaphorin Sema6A. We found that plexin-A2 deficiency causes a shift of mossy fibers from the suprapyramidal region to the infra- and intrapyramidal regions, while plexin-A4 deficiency induces inappropriate spreading of mossy fibers within CA3. We also report that the plexin-A2 loss-of-function phenotype is genetically suppressed by Sema6A loss of function. Based on these results, we propose a model for the lamina-restricted projection of mossy fibers: the expression of plexin-A4 on mossy fibers prevents them from entering the Sema6A-expressing suprapyramidal region of CA3 and restricts them to the proximal-most part, where Sema6A repulsive activity is attenuated by plexin-A2.
Suto
Fumikazu
F
Division of Developmental Genetics, National Institute of Genetics, Mishima 411-8540, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
Tsuboi
Miu
M
Kamiya
Haruyuki
H
Mizuno
Hidenobu
H
Kiyama
Yuji
Y
Komai
Shoji
S
Shimizu
Masayuki
M
Sanbo
Makoto
M
Yagi
Takeshi
T
Hiromi
Yasushi
Y
Chédotal
Alain
A
Mitchell
Kevin J
KJ
Manabe
Toshiya
T
Fujisawa
Hajime
H
D000818:Animals; D000831:Animals, Newborn; D001485:Basement Membrane / Q000502:physiology*; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000502:physiology*; D039961:Semaphorins / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018683:Excitatory Amino Acid Agents; D009419:Nerve Tissue Proteins; C492113:Plxna2 protein, mouse; C492110:Plxna4 protein, mouse; D011956:Receptors, Cell Surface; C504203:Sema6a protein, mouse; D039961:Semaphorins