The role of NG2 cells in axonal growth

NG2 cells are a novel and unique glial population in the developing central nervous system (CNS). In the developing or regenerating CNS, numerous NG2 cells are located in close proximity to neurons, and they could regulate axonal growth and guide navigating growth cones. The findings that the NG2 proteoglycan, a molecule expressed on the surface of NG2 cells, is inhibitory to growing axons have generated a widespread concept that NG2 cells also exert similar negative effects on extending axons. On the other hand, recent studies demonstrating that axonal terminals form functional synapses on NG2 cells at the various regions in the mature CNS suggest that NG2 cells are not repulsive to axons. To resolve this conflict and extend our knowledge on the functions of NG2 cells in development, physiology and pathology, I have investigated the role of NG2 cells in axonal development in this thesis study. I have shown for the first time that extending axons do not turn away, but form extensive contacts with NG2 cells in their projecting pathway and that the axonal growth is promoted by NG2 cells. In addition, elevating the level of the NG2 proteoglycan on NG2 cells did not reduce either the growth cone contact on NG2 cells or the growth promoting effect of NG2 cells. Finally, I showed that NG2 cells possess gelatinase activity, which could play a role in axonal growth. As a recently identified major glial population, NG2 cells are likely to play an essential role during CNS development and regeneration by positively interacting with growing axons. This study elucidated the effects of intact NG2 cells and the levels of NG2 proteoglycan in the context of NG2 cells on growing axons. Contrary to the prevailing notion, my results indicate a growth promoting role for NG2 cells regardless of the level of the NG2 proteoglycan. Findings from this work provided insight into the functions of NG2 cells in CNS and expanded our knowledge in understanding the mechanisms that regulate CNS pathway formation.