Reelin’s Roles In The Pathfinding Of Perforant Fibers And Commissural Fibers

Since discovered Reelin,it has been a hot topic in the field of neurodevelopmental biology for the role of Reelin and Reelin signaling pathways in the development of mammalian central nervous system.Reelin,a large glycoprotein,has different biological functions at different stages of mammalian development.Reelin as a signaling protein which maintain the stability of radial projection neurons migrate and guides tangent migration,and in regulating the projection and accurate positioning of the neuronal migration process plays an important role.Meanwhile,reelin also participates in the mammalian brain formation of neocortex stratification,the stability of the brain structure,and the formation of commissural fibers.Reelin signaling pathway or reelin mutations or abnormalities could cause a variety of nervous system disorders,such as cerebellar hypoplasia,lissencephaly,still could cause a large number of neurological development mental disease and neurodegenerative diseases.Though most recent researches focus on Reelin in the central nervous system’s role in the process of development,but the role in the pathfinding of perforant pathway and commissural fibers has not been able to cause enough attention.Therefore,in this paper,we compared the pathfinding of perforant fibers and commissural fibers development in wild-type mouse and Reeler mouse by immunofluorescent labeling technology and DiI and DiO tracing anterograde and retrograde in order to explore the role of Reelin protein in the pathfinding of perforant fibers and commissural fibers.Objective: In order to understand Reelin’s roles in the pathfinding of perforant fibers and commissural fibers between wild-type(WT)and Reeler mice were compared.Methods: Total 123 cases of WT mice and Reeler mice from embryonic day 16(E16)to postnatal day 7(P7)were used for this study.The perforant fibers and commissural fibers were labeled with DiI and DiO tracing(anterograde and retrograde).Nissl staining was also used to observe the histogenesis of the spinal cord,the cerebral cortex and hippocampus.Results:(1)Perforant fibers were mainly projected from the neurons in the layers Ⅱ to Ⅳ of entorhinal cortex,then they entered the stratum lacunosum-molecular layer in hippocampus proper as early as embryonic day 16(E16),while the perforant fibers reached the dentate gyrus(DG)at P1.Finally,the perforant fibers terminated in the outer two thirds of the molecular layer of the dentate gyrus at postnatalday 7(P7).Compared with WT mice,the perforant fibers in Reeler mice developed retardantly and distributed in disorder.(2)Fornix commissural fibers rose from the pyramidal cells of the CA3,hilus neurons and the Ⅱ-Ⅳ layers neurons of the entorhinal cortex at E16.Compared with WT mice,Reeler mice almost have no significant difference in the development of fornix fiber.(3)Corpus callosum was mainly projected from the neurons of layersⅡ-Ⅳ of in neocortex and corpus striatum,which started to project toward contralateral cortex at E18 and reached the contralateral striatum at P3.However,the corpus callosum fibers of Reeler mice entered to the contralateral neocortex later than in WT mice.Conclusions:(1)Reelin may be as a guiding cue for the development of perforant pathway and commissural fibers.(2)Without Reelin,the commissural and perforant pathways will develop retardantly,(3)the commissural and perforant pathways original neurons in cortical plate are in disorder.