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

Mol Biol Rep. 2020 Jul;47(7):5323-5331. doi: 10.1007/s11033-020-05614-0. Epub 2020 Jun 27.

Abstract

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.

Keywords: Cerebellum; IgG FC receptors; Mice; Microglia; Purkinje cells; Reelin.

MeSH terms

  • Acid Phosphatase / genetics
  • Animals
  • Apolipoproteins E / genetics*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Movement
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Purkinje Cells / metabolism*
  • Purkinje Cells / physiology
  • Receptors, Fc / genetics*
  • Receptors, Fc / metabolism
  • Reelin Protein
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / metabolism
  • Signal Transduction
  • White Matter / metabolism

Substances

  • Apoe protein, mouse
  • Apolipoproteins E
  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, Fc
  • Reelin Protein
  • Acid Phosphatase
  • Acp2 protein, mouse
  • RELN protein, human
  • Reln protein, mouse
  • Serine Endopeptidases