Glial cell fate determination in the visual system

In the optic system, optic nerve oligodendrocyte precursors (OPCs) are believed to originate from a focus of progenitor cells at the floor of the 3rd ventricle. These cells and/or their progeny then migrate along the optic nerve and form myelin around the optic nerve. However, the retina of most of the rodents is not myelinated. In this thesis the cellular and molecular mechanisms that regulate the early induction of OPCs at the floor of the third ventricle in chick and mouse, and the lack of oligodendrocytes in the mouse/rat retina were elucidated.;Optic nerve OPCs are derived from neuroepithelial cells in the floor of the third ventricle as a result of inductive signals from retinal ganglion cell (RGCs) axons. Coculture studies of embryonic chick retina and age matched dorsal spinal cord explants resulted in robust induction of OPCs from the dorsal spinal cord explants. A compartmentalized culture system demonstrated induction of OPCs by RGCs neurites. Early removal of eyes significantly reduced the number of OPCs in the floor of the ventricle. The induction of OPCs by RGCs axons is dependent on both sonic hedgehog (Shh) and neuregulin signaling. The axonal induction of OPCs is not a property specific to Chick RGCs, since reduced numbers of OPCs were observed at the floor of the third ventricle of Ocular Retardation (orJ) mice which have no optic nerves.;Oligodendrocytes are not present in murine retina. Conditioned medium of the embryonic retina inhibits differentiation of OPCs not only from multiple neural stem cells but also from optic nerve O-2A progenitor cells. The inhibition was partly mediated by BMPs signaling and strong BMP4 expression was detected at the optic nerve/retina junction. Embryonic retina progenitor cells are not able to differentiate into OPCs even in the presence of inductive signals and injection of a BMP inhibitor into the postnatal eyes also failed to induce retinal-derived oligodendrocytes.;Based on these data, I propose that the induction of OPCs in the optic system is dependent on signals from RGCs axons, and that oligodendroglia fate determination is decided by both intrinsic and extrinsic mechanisms.