Formation of a functional nervous system requires the coordinated interactions of several types of cells derived from distinct precursor populations. These cells must often migrate great distances, identify each other and coordinate their differentiation. This ensures that information can be passed between the central nervous system (CNS) and peripheral nervous system (PNS) targets via peripheral nerves. Investigating the cellular and molecular mechanisms that mediate motor nerve formation will provide important insights into the developmental programs that assemble and maintain functional nervous systems.

The long-term goal of the work in the lab is to understand the development of spinal motor nerve components and how cell-cell interactions result in coordinated differentiation, myelination, maintenance and regeneration of nerves. To begin to address these developmental paradigms, we use zebrafish as a model system because it uniquely provides the opportunity to combine in vivo, time-lapse imaging with genetics.

Tg(nkx2.2a:megfp);Tg(sox10(7.2):mrfp) larva at 3 dpf. Schwann cells are in red and perineurial glia are in green.Current research in the lab is focused on investigating the developmental programs that mediate motor nerve development, maintenance and regeneration. Specifically, we would like to identify the molecular mechsnisms that mediate the interactions between perineurial glia and Schwann cells during spinal motor nerve development. Schwann cells and perineurial glia are derived from distinct precursors but meet at motor nerves and coordinately differentiate as they ensheath. Preliminary data indicate that these coordinate interactions are essential for motor nerve development. Therefore, we hypothesize that sequential and reciprocal interactions are required for differentiation of Schwann cells and perineurial glia along spinal motor nerves. Currently, very little is known about how glial cells communicate in the PNS. This work will begin to address questions like: How are the developmental programs of spinal motor nerve components coordinated? and What are the specific genes and their roles in motor nerve development? From these results we will be able to characterize how perineurial glia and Schwann cells interact during spinal motor nerve formation and how these early interactions result in the development of the PNS and what roles they might play in disease and/or injury.

In the future, we are interested in determining the role of perineurial glia in spinal motor nerve maintenance, disease and regeneration. Considerable growth occurs during juvenile stages after motor nerves have been formed and myelinated. Therefore, motor nerves are constantly remodeled. This remodeling, which occurs during a period still tractable for imaging and genetic manipulations, provides an exceptional model for nervous system maintenance. Using genetic ablation coupled with in vivo imaging, we will investigate the role the perineurium plays in spinal motor nerve maintenance and regeneration in juvenile and adult fish.