The role of cell adhesion molecules and Bergmann glia in Purkinje cell monolayer formation
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Date
2020-08
Authors
Shabanipour Dehboneh, Shahin
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Abstract
ABSTRACT
Purkinje cells (PCs) are large neurons in the cerebellar cortex with elaborate dendrites that receive inputs into the cerebellum. Being the only output of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement to social activities. Many cerebellar disorders are partly characterized by dysfunction/death of PCs without any effective treatments. Developing treatments relies on understanding early neurodevelopmental process. In this study, I investigate the migratory behavior of PCs in postnatal mice. Despite the current modes of neuronal migration that have been introduced so far, the main underlying mechanism of dispersing PCs from the cluster stage to the monolayer position is still unclear. I hypothesize that Bergmann glia cells (BGCs) play a crucial role for PCs postnatal dispersal and monolayer formation. To test the hypothesis, I used a mouse model of excessive PCs migration, naked ataxia (nax; Acp2 -/-), and investigated the expression pattern of genes which are potentially necessary to hold both cells together during migration. A group of most promising cell adhesion molecules were selected to study in nax and wt sibling mouse cerebellum. The expression of adhesion molecules was measured and visualized by western blot and IHC respectively. To clarify the contribution of protein values to the targeted cells, qRT-PCR was carried out on whole cerebellum and isolated PCs and BGCs from two different postnatal days. It is speculated that the characteristics of all four studied CAMs along with profile of their expression in BGCs strongly supports the possibility of BGCs-PCs connection at P2 and P7. However, the migration of BGCs as a carrier of PCs seems to be differently affected by the CAM members. Among all studied CAMs only the expression pattern of Ncam1 and Cdh4 is more in line with my hypothesis. Therefore, it is concluded that Ncam1 and Cdh4 are potentially involved in BGCs-PCs attachment, regulating the coupled migration and forming PCs monolayer in cerebellar cortex.
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Keywords
Cerebellar cortex, Purkinje cell, Bergmann glia, Cell adhesion molecules, Migration