Interactions between Plexin-A2, Plexin-A4, and Semaphorin 6A Control Lamina-Restricted Projection of Hippocampal Mossy Fibers.

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Suto, Fumikazu | Tsuboi, Miu | Kamiya, Haruyuki | Mizuno, Hidenobu | Kiyama, Yuji | Komai, Shoji | Shimizu, Masayuki | Sanbo, Makoto | Yagi, Takeshi | Hiromi, Yasushi | Chédotal, Alain | Mitchell, Kevin J | Manabe, Toshiya | Fujisawa, Hajime

Edité par CCSD ; Elsevier -

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.

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