Although neural stem cells (NSC) have been isolated successfully and characterized relatively extensively, little is known about the role of their natural microenvironment, the so-called niche, in influencing their behavior. The role of distinct niche signals and their spatial orientation in regulating the choice between quiescence, self-renewal or differentiation is poorly understood, due in part to a lack of suitable in vitro model systems. The main goal of the proposed project is to investigate how extracellular signals affect symmetric/asymmetric cell division of single neural stem cells. This will be achieved by generating artificial microenvironments recapitulating key biochemical and structural characteristics of stem cell niches, that allow to expose NSCs to a variety of protein signals in a spatially-controlled fashion, and allow high-throughput tracking of single stem cells by time-lapse microscopy and retrospective fate analysis. Understanding the basic mechanisms that regulate the balance between self-renewal and differentiation of tissue-resident stem cells will open up new opportunities for their clinical application.