Recent studies examining cell-cell interactions during CNS development and following disease or trauma have highlighted our limited understanding of the in vivo functions of the myelinating cell of the CNS, the oligodendrocyte. With this in mind, our laboratory has developed techniques by which a profile of proteins derived from or regulated by oligodendrocytes can be elucidated. Specifically, we have demonstrated that oligodendrocytes can be selectively eliminated from one optic nerve of a rat by treating the animal with a unilateral exposure of X-irradiation at the time of birth. Consequently, this approach allowed us to experimentally create, within the same animal, one optic nerve devoid of oligodendrocytes and their progenitors (the X- irradiated side) and one optic nerve containing the normal oligodendrocyte population (the untreated side). Using this experimental animal model we hypothesized that uncharacterized proteins, derived from and regulated by oligodendrocytes, which are crucial for CNS development can be identified. Specifically, by comparing protein profiles found within the normal myelinating optic nerve versus the X-irradiated optic nerve, where oligodendrocytes are absent, potential oligodendrocyte-derived proteins can be quickly identified. Further verification that these proteins are indeed related to oligodendrocytes and/or the processes of myelination can be obtained by their reappearance in the 2-D gel protein profile of P28 X-irradiated nerves that, as we have shown previously, undergo a delayed myelination. We then employed mass spectrometric analysis to determine the identities of oligodendrocyte derivedregulated proteins. In this thesis, I will begin by describing our current knowledge of the proteins expressed by oligodendrocytes and their role(s) in oligodendrocyte function. This will be followed by a detailed description of the experimental model system we utilized in an attempt to elucidate the complete repertoire of oligodendrocyte-regulated proteins. We will then describe the results generated fiom our methodology and discuss the implications of our findings in relation to the functional cooperation between oligodendrocytes and other cells of the developing central nervous system. The results generated fiom this project should lead to a clearer understanding of the role of oligodendrocytes and'of the array of proteins whose expression patterns are associated with these cells during CNS development.