Characterization of peripheral satellite glial cells and their effects on axon regrowth following injury in a zebrafish developmental model

During embryonic development, migratory neural crest cells give rise to the
vast majority of neurons and glia in the peripheral nervous system (PNS). Among these differentiated cell types are specialized glia known as satellite glial cells (SGCs). SGCs distinctively ensheathe the cell bodies of neurons in PNS ganglia, including dorsal root ganglia (DRG) which house sensory neurons responsible for the sensations of temperature, touch, and pain. SGCs perform critical functions within the DRG such as supporting neuronal homeostasis, regulating molecular composition of the extracellular environment, and relaying key intercellular signaling pathways. Given the intimacy between SGCs and sensory neurons, much work has sought to characterize how SGCs may amplify or attenuate the emergence of peripheral pain disorders. However, our knowledge of this system is primarily limited by the biological constraints of adult mammal and cell culture models. Consequently, we know very little about SGCs, how they respond to different injury modalities during development, and how these responses influence axonal regrowth. In this dissertation, I use larval zebrafish (Danio rerio) to study SGC function in vivo within DRGs. I will first introduce a review of the morphological and molecular characteristics of SGCs throughout the PNS and their responses to neuronal damage. I then present a novel transgenic system for the study of SGCs and other peripheral glia throughout zebrafish development. I then demonstrate how the early SGC response to DRG central branch ablation impairs successful axon regrowth. This work fills gaps in our understanding of neuron-glia interactions and SGC functionality, laying the foundation for a new model to investigate glial-based mechanisms of peripheral neuron damage, dysfunction, and disease.