Oligodendrocyte Progenitor Cell Tiling

During vertebrate development, oligodendrocyte progenitor cells (OPCs) are specified from gliogenic precursors in the central nervous system (CNS) after neurogenesis. Following specification, OPCs begin a complex process termed tiling that results in OPCs becoming evenly dispersed and occupying non-overlapping territories throughout the CNS. Developmental OPC tiling is comprised of three main components, namely, migration, proliferation, and contact-mediated repulsion (CMR). A few foundational studies have thoroughly characterized these OPC tiling behaviors, however, little is known about how these behaviors interact to result in OPCs being evenly distributed throughout the CNS.

In this dissertation, I begin by providing a comprehensive review of the molecular mediators currently understood to influence the individual behaviors of OPC tiling. I then propose a unified theory of how OPC tiling behaviors interact to produce the emergent property of uniform OPC dispersal throughout the CNS. Then, using zebrafish as a vertebrate model, I demonstrate the first in vivo investigation into the role of the Met signaling pathway in regulating OPC tiling, primarily focused on its role in mediating migration and proliferation. Finally, I present evidence regarding other molecular mediators that contribute to developmental OPC tiling and delineate the open questions that remain in our understanding of OPC tiling.

This work fills a gap in our understanding of molecular signaling pathways involved in regulating developmental OPC tiling, which lays a foundation for future investigation into adult tiling and understanding OPC behaviors in disease and injury-response.