Cellular Communication and Mechanobiology in the Developing Dorsal Root Ganglia

Communication between cells is necessary for the proper formation of tissues. The nervous system is no exception. During development of the nervous system, neurons and glia are in constant communication as they form a functional network of cells. Neurons communicate over great distances to provide sensory perception and reactions for the body. Glia modulate neuronal activity and provide support to neurons. The communication between these cells is most described through chemical signaling. While neurons and glia are communicating during development, the surrounding environment often changes causing additional signals to act on these cells. Amongst these signals are mechanical forces. Because communication between neurons and glia is key to proper function and health, it is important to investigate not only chemical signaling, but also mechanical signaling in development.

In this dissertation, we use confocal time-lapse imaging, calcium imaging, pharmacological manipulation, and genetic manipulations in zebrafish to investigate communication between neurons and glia during development. The construction of dorsal root ganglia (DRG) is used as a model to study these processes. We first utilize calcium imaging to identify the formation of glial networks via synchronous calcium transients in the developing DRG. We then use a combination of pharmacological and genetic manipulations to identify roles of mehanosensitive ion channel, Piezo1, in DRG development. This work identifies that mechanobiology impacts the calcium signaling of DRG glia during development, which impacts its construction. In addition to this work, we also investigate the calcium signaling in cellular communication following injury, calcium signaling in cell proliferation, and identify intercellular calcium waves in the DRG. Together this work identifies molecular machinery involved in distinct forms of calcium signaling between cells and provides insights into further utilities of calcium imaging in the developing DRG.