The spindle is a microtubule (MT)-based highly dynamic molecular machine that mediates precise chromosome segregation during both mitosis and meiosis. To form a spindle, centrosome-containing cells exploit microtubules (MTs) nucleated by the centrosomes and MTs generated near the chromosomes and at the kinetochores. We plan to identify and characterize the genes/proteins required for kinetochore-driven MT growth using Drosophila S2 cells as a model system. Given that most Drosophila mitotic proteins are evolutionarily conserved in mammals, our studies are likely to provide novel insight into the mechanisms of spindle formation in human cells, with a possible impact on cancer therapy. I will describe our approach in detail and present our results on some factors that regulate chromosome-induced MT formation.