Novel Roles of Glial Precursors in Early Neurogenesis

During vertebrate embryonic development, the ectoderm-derived neural plate along and anterior-posterior axis rises and folds into the neural tube. Neuroepithelial cells inside the neural tube proliferate and ultimately differentiate into neurons and glia in the central nervous system (CNS). Neural crest cells (NCC) specified at the border of the neural plate undergo an epithelial to mesenchymal transition and delaminate from the neural epithelium upon the folding of the neural tube. Subsequently, NCCs migrate through the periphery and give rise to most neurons and glia in the peripheral nervous system (PNS). However, as an exception, perineurial glia associated with PNS nerves derive from the floorplate in the spinal cord. Their CNS precursors migrate to the periphery through motor exit point transition zones, where spinal motor neuron send axons to the PNS. Over the past decades, the specification and differentiation of neurons and glia from precursor cells during embryogenesis have been studied extensively as a fundamental question in neurogenesis. However, how these cells coordinate with each other during neural development to ensure the correct patterning of the nervous system is poorly understood.

In this dissertation, using zebrafish embryos as a model organism, I demonstrate novel roles of two types of glial precursors, perineurial glial precursors and neural crest cells, in directing motor axon pathfinding out of the spinal cord and phagocytosing cellular debris in the CNS and PNS, respectively. This work not only fills gaps in our knowledge about nervous system assembly, but also sheds light on the under-appreciated but essential roles of precursors cells besides giving rise to their derivatives.