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

2007; Cell Press; Volume: 53; Issue: 4 Linguagem: Inglês

10.1016/j.neuron.2007.01.028

1097-4199

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

Hippo pathway signaling and YAP/TAZ

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.