Glial Cells at the Border of the CNS During Development and Disease

The boundary of the central (CNS) and peripheral (PNS) nervous system critically functions to provide immune protection to the CNS. Although the nervous system is physically separated into the CNS and PNS domains by a thick protective barrier of glial cells, it is crucial for these two distinct systems to be successfully connected in order to transmit information efficiently and maintain a healthy and functioning nervous system. Specialized neural and glial populations reside within the CNS or PNS to facilitate the proper organization of these systems to effectively communicate information across the CNS/PNS boundary. Despite our understanding of the importance of this protective CNS boundary, little is known about how the CNS boundary is constructed and organized during normal development. Consequently, in instances of disease or injury where the CNS/PNS boundary becomes disrupted, the resulting disorganization prevents neuronal information from being properly communicated to preserve a fully functional nervous system. This presents a significant gap in our understanding of normal CNS boundary development and further how to reconstruct this crucial boundary during injury and disease. Until we understand the cellular interactions and cues involved in normal boundary development, we cannot begin to fully understand how to rebuild and replicate this boundary organization in neurodegenerative disease states like Multiple Sclerosis (MS) and symptoms resulting from neuronal injuries like neuropathic pain.

Further characterization of the specific interactions between CNS and PNS-resident cells like neuron-glia interactions is necessary to fully understand how to organize the boundary during development. These specific interactions occurring at the boundary are understudied. In this dissertation, we will describe several novel interactions between PNS and CNS cells at the CNS boundary uniquely using in vivo time-lapse imaging of intact developing zebrafish. We will identify and explore three distinct roles of specialized glial cells in the CNS that traverse the CNS/PNS boundary. First, we describe a unique interaction between a peripheral neuron population and a functionally distinct CNS-resident glial progenitor population. Next, we identify a distinct population of glial cells that override their CNS-resident domain specific nature following developmental injury. Lastly, we identify and characterize a population of glial cells that colonize the CNS in early embryonic development. Together, this work expands on our current understanding of the interactions between the CNS and PNS cells that aid in the construction of the CNS/PNS boundary during normal development and homeostasis. This work additionally advances our gap in understanding of how glial cells organize and interact during boundary disruption and disorganization following states of injury and disease. and further reveals crucial roles CNS and PNS cells play in reconstructing this crucial immune protected CNS/PNS boundary.