The Morphological Study That Reelin Regulates The Development Of Rostral Migratory Stream(RMS) Of Mouse

As a kind of specific stem cells, neural stem cells can produce other cells and generate the neural tissue by way of asymmetric division because of its self-renewal ability. The mature incubation, migration and differentiation of neural stem cells is closely related to the development of the central nervous system, which is very important to understanding the development, damage and its repair mechanism of the nervous system. The proliferation and mature incubation of neural stem cells is the basis of individual growth and development; The directional migration of neural stem cells is the prerequisite of nervous system development in the embryonic period, development of individual and repair of tissue damage is dependent on the directional migration of neural stem cells; After migrating to specific zone, neural stem cells divide into particular cells to play its function on the regulation of a series of molecular signals, and then, differentiation of neural stem cells provides a necessary condition for formation and development of different organs and perfection of their function. So far, two kinds of cell migration patterns are certained: radial migration and tangential migration. As a highly restricted channel of neural stem cells in SVZ migrate to the olfactory bulb, Rostral Migratory Stream(RMS) is considered by Doetsch to be aggregated by Subventricular Zone(SVZ) from the back to former throughout the wall of lateral ventricle ependymal Zone. As a typical example of tangential migration, RMS is the best model to study tangent migration. As a regulatory signal of “go” and “stop” of cell migration, Reelin induce intracellular effector Dab1 phosphorylation through combination with its Receptors-Apolipoprotein E Receptor 2(ApoER2) and Very Low Density Lipoprotein Receptor(VLDLR) so that the migration cells fall off from their support – the fiber of radial glial cells, then locate following the “inside – out” pattern and form six cortical layer structure at last. As an important signal, Reelin plays a very important role on cell migration, cortical lamination and development of cerebral cortex. Abnormal synthesis or disorder secretion and even lack of Reelin protein will lead to a series of mental system diseases, such as schizophrenia, temporal lobe epilepsy, autism and so on, so understanding the influence of Reelin on the development of the nervous system has a certain basis meaning, which can provide support for the treatment of mental disease.For a long time, people do a lot of work about Reelin in the radial migration, but the role of Reelin in RMS is unclear. Therefore, Wild type(WT) mice and reeler mice were used for immunofluorescent labeling, ink perfusion and ultrastructure observation, therefore, neural stem cells, the radial glial cells and vasulature in neocortex and RMS would be visualized and the development of RMS in two groups would be compared.Objective: To investigate the differentiation of neural stem cells in the subventridular zone(SVZ) and neural migration along the the rostral migratory stream(RMS) into the olfactory bulb(OB). Particularly, regulation of Reelin on the neural differentiation and migration in RMS will be explored.Methods: Wild type mice(50 cases) and reeler mice(23 cases) from E16(embryonic day 16) to P90(postnatal day 90) were used for nissl staining, immunofluorescent labeling, ink perfusion and ultrastructure observation, therefore, neural stem cells, the radial glial cells and vasulature in neocortex and RMS would be visualized.Results: In the early period to was born, vascular niches in the SVZ consisted of lots of neurons, glial cells, neural stem cells and vascular vessel which provided a ideal microenvironment for the differentiation and mturation of neural stem cells. After maturation in the vascular niche, the neural stem cells started to migrate tangentially along RMS toward olfactory bulb with the chain-guidable pattern along both glial and vascular scaffold. After entering in OB, the migrating pattern translated into the radial migration, and these cells would differentiate into various neurons in olfactory bulb. In general, development of RMS, neural stem cell differentiation and cell migration in reeler mice were similar to wild type, howover, the distribution of vasculature in cortex and RMS was disorder, and migrating cells often concentrated in olfactory bulb densely and scatteredly.Conclusions: Niche in subventricular zone is the main sources of neural stem cells, and both vasculature and radial glia acts as scaffold for the migration of neural stem cells in RMS. As an important signal for cell migration, Reelin can affect the development of blood vessels and cell migration in RMS. Withpot Reelin, the cell migration in RMS will be blocked.