The Role Of Reelin In The Evolution Of Central Nervous System

Over the past decade, the relationship between Reelin signaling pathway and the evolution of the central nervous system cortical has been a hot issue in the field of neurobiology. Reelin protein as a "start and stop" signal that regulates nerve cell migration, plays a particularly crucial role which maintains the normal development of the cerebral cortex and the normal functioning of the central nervous system. Reelin signaling pathway or reelin gene mutations or abnormalities cause a large number of nervous system disorders: schizophrenia, autism and so on. Though most study focused mainly on the Reelin'role in the central nervous system development, therole and relevant regulatory mechanisms of Reelin signaling pathway in central nervous system evolution is rare. In this paper, we compared formation of tubular nervous system, archicortex and neocortex development in wild-type mouse and Reeler mouse by immunofluorescent labeling technology in order to explore the role of Reelin protein in the cortical evolution.Objective: To investigate Reelin's role in the evolution of the central nervous system and the relevant regulatory mechanisms.Methods: Wild-type(WT) and reeler mice(total 192 cases) from E16(Embryonic day 16) to P30(postnatal day 30) were used for this study. The neuronal migration, radial glial cells and neuroproliferation in the cerebral cortex, hippocampus and spinal cord were visualized by immunofluorescent labeling, 5-Bromodeoxyuridine immunofluorescence(BrdU method). Nissl staining was also used to observe the histogenesis of the spinal cord, the cerebral cortex and hippocampus.Results:(1) During the development of spinal cord, the first neuronal migrate occurred from neuroepithelium to form H-like gray matter. Compared WT mice with reeler mice, only nuance was found in histogenesis, cell migration, radial glia and neuropliferation.(2) On the other hand, the development of hippocampus required second neural migrations to eventually form the pyramidal cell layer and granule cell layer with double "C"-like shape. Compared with WT mouse, pyramidal layer in the reeler mouse was splitting into two layers with the disorder of migration and proliferation. In addition, the limitation of granule layer and hilus gradually disappeared to form drumstick-like structure. In the meantime, the number of proliferative neural stem cells reduced and the radial glial cells were arranged in disorder.(3) The formation of the neocortex also required second neural migration to form six-layer cortex with inside-out migration manner. Compared with WT mouse, lamination of neocortex in the reeler mouse was in disorder. The neuroproliferation and radial glial cells reduced, and the radial glial were arranged in disorder.Conclusions:(1) Reelin almost does not take participate in first migration of neural cells in spinal cord.(2) Reelin's important function probably is involved in second migration and cell proliferation to affect the formation of cortical plate.(3) Reelin may be a key molecule during CNS evolution.