The role of glial-glial interactions during oligodendrocyte tiling

University Of Virginia, Charlottesville VA

Investigators

Abstract

ABSTRACT The development of an efficient nervous system is contingent upon the differentiation and proper organization of billions of glia in the central and peripheral nervous systems (CNS and PNS, respectively). As neurodevelopment progresses, glial cells communicate with their neighbors to proliferate, migrate, and establish non-overlapping territories – a process termed glial tiling. Oligodendrocyte lineage cells (OLs) are a glial population that must spread throughout the CNS by tiling. However, the cellular and molecular mechanisms that orchestrate OL tiling remain unclear. Previous data from our lab implicates Met signaling as a key regulator of OL migration. Here, using genetic mutation, endogenous knock-in techniques, and live confocal imaging, I will elucidate the phenotype of hgf knockout, identify the source of Hgf secretion, and reveal potential glial-glial interactions that drive OL dorsal migration. Genetic manipulation and cellular ablation assays will further reveal the temporal requirements and sufficiency of Hgf signaling during OL migration. To identify additional mediators of OL tiling, I turned to single nuclei RNA sequencing datasets and identified the cell adhesion molecule, Dscamb, as highly upregulated in pre-myelinating OLs. Using full body and cell-type specific mutagenesis techniques, I will investigate the role of dscamb during proliferation and contact mediated repulsion of OLs. OL-OL interactions and OL-MEP glia interactions will be examined by live confocal imaging when dscamb is genetically perturbed. Lastly, I will investigate the dosage effects of dscamb by overexpressing the gene in specific cell types. Together, these studies will provide insight into how glia communicate with one another to pattern the developing nervous system.