Investigating the role of microglia in myelin development

Abstract

We investigate the role of microglia in myelin development. Myelination is an essential process in early development that consists of the ensheathment of axons by myelin, which ensures rapid conduction of action potentials. Although myelination is predominantly driven by oligodendrocytes, the other glial cells, including microglia also contribute to this process. Microglia are resident immune cells in the central nervous system (CNS) and carry out important functions not only in injury and disease but also in homeostatic conditions. While the role of microglia in myelination has been explored by previous studies, little is known about the precise mechanism. Recently, a distinct microglia subset characterized by high expression of Spp1, Gpnmb, and Igf1 was found in white-matter regions in the early post natal brain but not at other time points. First, we developed a novel constitutive Cre mouse line, Fcrls-Cre, using the CRISPR-Cas9 system to target all subsets of microglia, including the white matter-associated microglia. Second, we focused on a signaling pathway triggered by ligand IgG and the gamma chain of its receptor, FcRg, and investigated their roles in the development of myelin. Our study hopes to provide a valuable tool to study microglia in vivo and to increase the understanding of how microglia contributes to myelin. In the Appendix, I present a brief review of the promises and challenges of CRISPR in gene therapy in hopes to inform the discussions on the economic, ethical, and regulatory implications of gene editing.