Molecular Mechanisms of Myelinating Glial Cell Development

Myelination of large diameter axons facilitates rapid neurotransmission, provides trophic support to axons, and aids in plasticity that contributes to learning and memory. During development and in adulthood, myelin is produced and maintained by myelinating glial cells, including oligodendrocytes, Schwann cells, motor exit point glia, and cochlear satellite glial cells. Despite the importance of myelin, we still don’t understand the full repertoire of molecular mechanisms that regulate myelinating glial cell development. In this dissertation, we identify several candidate genes, including cluster of differentiation 59 (cd59), C-X-C motif chemokine ligand 14 (cxcl14), peroxiredoxin 1 (prdx1), and annexin 13, like (anxa13l), that are highly expressed in myelinating glial cells but have limited data on their function in the developing nervous system. Looking closer at Cd59, we demonstrate that developmental inflammation stimulates Schwann cell proliferation and that Cd59 helps regulate this process, which is necessary for normal myelin and node of Ranvier formation. This work uncovered part of the molecular network that facilitates myelinating glial cell development as well as highlighted the intimate relationship between the immune and nervous systems that contributes to nervous system development. Furthermore, this study produced several tools and new hypotheses that will help expand our knowledge of myelinating glial cell development, which will ultimately better our understanding of nervous system development and aid in future treatments for patients, such as those with CD59 dysfunction.