Mutations in the Reelin pathway are associated with abnormal expression of microglial IgG FC receptors in the cerebellar cortex.

Maryam Rahimi-Balaei, Xiaodan Jiao, Azadeh Dalvand, Shahin Shabanipour, Seung H Chung, Shayan Amiri, Jimig Kong, Hassan Marzban

Molecular biology reports 2020 Jul

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Microglia are the immune cells of the central nervous system involved in a variety of developmental processes, such as regulation of cell death and survival, spatial patterning, and contribute to the development of Purkinje cells (PCs) during migration. Microglia express immunoglobulin G Fc receptors (FcgRs). In this report, we describe microglial FcgR expression and its relation to abnormal PC migration in the cerebellum during development. To detect microglial FcgR, the direct anti-IgG (secondary antisera) and high concentrations of Triton X-100 were applied as a method for labeling microglial cells without the use of any specific primary antiserum. By using Acp2-/- mice, which show an excessive PC migration into the molecular layer (ml), and 3 different types of mice with a null to alter the Reelin pathway (Reeler-, Dab1 (SCM)-, and Apoer mutant mice), we studied the location of PCs and the expression of FcgRs. Wild type littermates were used as controls in all studies. We show that the expression of microglial FcgRs was absent and PCs were ectopically located in the white matter in the cerebella of all mutant mice, except for the Acp2-/- mice (PCs were located in the ml). These results suggest a role for FcgRs in the Reelin signaling pathway, not in regulating PC migration, but rather in the adaptation to an environment with a relatively large number of ectopically located PCs. However, the exact correlation between the ectopic location of PCs and lack of FcgRs in Reeler, SCM, and Apoer-/- mice and the presence of FcgRs and directed PC location in the ml in Acp2-/- mice are yet to be determined.

Citation

Maryam Rahimi-Balaei, Xiaodan Jiao, Azadeh Dalvand, Shahin Shabanipour, Seung H Chung, Shayan Amiri, Jimig Kong, Hassan Marzban. Mutations in the Reelin pathway are associated with abnormal expression of microglial IgG FC receptors in the cerebellar cortex. Molecular biology reports. 2020 Jul;47(7):5323-5331