Putative molecular mechanisms underlying stereotyped axonal pruning of the dentate gyrus infrapyramidal tract

Development of the nervous system requires proper neural connectivity of the axons to their targets. During development, the neurons make more connections than are necessary for normal adult function. Axon Pruning is a regressive event that allows for a formation of a proper neural connection by trimming the unnecessary connections. The establishment of this precise neuronal connection is a sequential process that involves axon initiation, growth cone navigation, target selection, synapse formation and, in specific brain areas, stereotyped pruning. Synapse elimination and axon pruning require reorganization of the neuronal cytoskeleton, however the mechanisms by which both processes occur are unknown. Riccomagno and colleagues (2012) linked the RacGAP β2-chimaerin in axon pruning of the hippocampal dentate gyrus’ (DG) infrapyramidal tract (IPT). The study showed that β2-chimaerin hydrolysis of rac1GTP is required for IPT pruning following semaphorin 3F (sema3F) signaling through its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor complex. Since, regulation of Rac1 signaling pathway involves WAVE, we hypothesize that inhibition of one or more of the rac1 downstream pathways leads to reorganization of the neuronal cytoskeleton such that stereotype axon pruning of the DG IPT. Proteins from brain tissues were separated by SDS-PAGE and levels of WAVE-1 were analyzed in the four main regions of the brain including cerebellum, cerebrum, midbrain and hippocampus in a time course study. Immunohistochemical studies were carried out on the hippocampus specifically covering postnatal days before, during and after pruning of the IPT. Western blotting and immunohistochemical studies show that WAVE-1 is present in the brain during the time to stereotyped axonal pruning