MOTOR EXIT POINT GLIA

Recent studies from the lab show that MEP glia myelinate spinal motor root axons in a discrete region located between oligodendrocytes, which myelinate spinal cord axons, and Schwann cells, which myelinate motor nerves. Currently, we are elucidating how MEP glia interact with oligodendrocytes and Schwann cells to myelinate distinct, non-overlapping peripheral axonal segments and the mechanisms that mediate these interactions. We are also investigating if we can divert MEP glia from spinal motor roots and take advantage of their myelinating property 1) in the spinal cord and 2) along more proximal locations of motor nerves in Schwann cell deficient zebrafish models. Finally, we previously showed that MEP glia express a range of markers including a combination of both CNS and PNS glial markers as well as one boundary cap cell marker. We are currently expanding this repertoire by using RNA sequencing.

OPC TILING

Oligodendrocytes myelinate central nervous system (CNS) axons in order to facilitate conduction of electrical impulses and provide protection from the surrounding environment. They are derived from oligodendrocyte progenitor cells (OPCs), which migrate throughout the developing CNS and become evenly distributed. While most OPCs mature into oligodendrocytes, a population of OPCs remains evenly distributed in the CNS throughout adulthood. This process of migrating throughout the CNS is termed OPC tiling and is defined by three hallmarks: migration, proliferation, and contact-mediated repulsion. Though, the process of tiling in OPCs has been well described, the molecular mediators for each hallmark, and how those mediators interact, is unknown.

PERINEURIAL GLIAL DEVELOPMENT

Previous studies from the lab show that during nervous system development, perineurial glia migrate out of the spinal cord through motor exit points (MEP) and ensheath motor axon-Schwann cell complexes, ultimately differentiating into the perineurium, a component of the blood-nerve-barrier. However, how perineurial glia are specified in the spinal cord and migrate through MEPs are still unknown. Our goal is to understand the early development of perineurial glia and identify the molecular mechanisms behind their migration through the CNS-PNS transition zone.

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GLIAL DIVERSITY

The peripheral nervous system (PNS) contains different types of glia with diverse functions such as myelinating peripheral axons, forming the perineurium and maintaining the boundary between the peripheral and central nervous system. These glial types arise from different locations, have different developmental behaviors, acquire different morphologies and express unique combinations of genes. Although we are beginning to understand how peripheral glia develop and know a few of the genes important for their function, the full molecular programs that regulate their specification, migration, differentiation and function are unknown. Furthermore, there is increasing evidence that there is a far greater amount of glial diversity in the PNS than previously appreciated. In order to determine the level of glial heterogeneity in the PNS, we are interrogating the transcriptomes of several PNS glial subtypes. These studies will not only help us understand more about how peripheral glia develop, but will also help us investigate the distinct roles and molecular changes that occur in specific glial populations following nerve injury and demyelinating diseases.

PERINEURIAL GLIA RESPONSE TO INJURY

Previous studies in the lab demonstrated that perineurial glia are essential mediators of peripheral motor nerve regeneration after injury. Following nerve injury, perineurial cells phagocytose debris and form a bridge across the injury gap prior to axonal regrowth. While our studies showed that this debris clearance and bridge formation by perineurial glia is essential for regeneration, the cellular and molecular mechanisms that underlie this process remain unknown. We are now interested in identifying the molecular mechanisms that mediate this essential regenerative process as well as elucidating the interactions that perineurial glia have with other cells, such as Schwann cells, following nerve injury.

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