Glial Cell Plasticity During Development and Myelinopathies

Forming a functional vertebrate nervous system requires intricate interactions amongst various cell populations, including neurons and glia. Diverse populations of glial cells, such as myelinating glia, i.e., oligodendrocytes of the central nervous system (CNS) and Schwann cells and motor exit point (MEP) glia of the peripheral nervous system (PNS), and perineurial glia, which form the blood-nerve barrier, comprise the nervous system. Myelin sheaths promote rapid and efficient communication between the CNS and PNS, and myelinopathies have a significant impact on nervous system function. Because of the functional deficits that can result following myelinopathies, it is imperative to develop a better understanding of the glial interactions and responses following myelin perturbations.

My work presented here provides a detailed characterization of glial-glial interactions during spinal motor nerve assembly, maintenance and in response to axonal injury, as well as glial responses following a demyelinating insult. First, I describe modifications made to a transmission electron microscopy (TEM) protocol that allows me to efficiently locate nervous system structures to investigate glial ultrastructure and morphology. Next, I use this TEM assay, in combination with in vivo imaging, immunohistochemistry and laser axonal transection and PNS barrier integrity assays to better characterize glial-glial interactions in response to a myelinopathy in which oligodendrocyte progenitor cells (OPC) ectopically exit the CNS to associate with peripheral axons. To investigate glial response following a demyelinating insult, I present data characterizing a novel focal demyelination model in zebrafish that I created to visualize myelin breakdown and repair in vivo. Taken together, this work provides a more comprehensive understanding about the remarkable plasticity of glial cells during nervous system development, maintenance and in response to myelinopathies.