The NG2-positive cells are the oligodendrocyte precursors, which, when terminally differentiated, are capable of myelinating the central nervous system. There is however an ever-growing list of evidences that NG2 cells actually possess an intrinsic neurogenic potential and they are capable of neuronal differentiation in response to environmental stimuli. To address the question, we have established a model of an indirect co-culture system of the freshly isolated rat neonatal NG2 cells and organotypic slices derived from two distinct CNS regions (hippocampus and spinal cord) to mimic the nervous tissue microenviroment. The cell differentiation in microenvironment of OGD-injured hippocampal slices has been studied as well. The molecular analysis of selected trophic factors has been performed to determine the patterns of their expression. Indeed, the comparison of the cell commitment and development in various microenvironments has pointed to significant dissimilarities. First of all, the medium being continuously conditioned by the hippocampal slices efficiently promoted neurogenesis. The effect has been significantly abolished in co-cultures with the injured tissue. The less pronounced susceptibility to adopting neuronal phenotype and the considerable slowdown of oligodendroglial development was observed in the co-cultures with the spinal cord slices. The role of BDNF in oligodendroglial progenitor commitment and development has been investigated proving that it is one of the key players in the examined processes. The specificity of the instructive clues cocktail might module the fate choice of mobilized endogenous or transplanted cells, which should be taken into consideration while planning neurorepair strategies.