Neurogenesis in the mammalian neocortex depends upon asymmetric cell divisions to maintain a balance between self-renewal and neuronal differentiation. This process is likely a key element governing the expansion of the human cerebral cortex, and its disruption can lead to severe developmental disorders such as microcephaly and lissencephaly. However, mechanisms of asymmetric cell division in mammalian brain development are largely unclear, and its potential role in human cortical development has not been examined. Substantial headway has been made in understanding mechanisms of asymmetric cell division in the Drosophila central nervous system. Our lab has recently published a genome-wide RNAi screen, which has identified several novel regulators of asymmetric cell division in Drosophila. To test whether these newly identified factors have conserved roles in mammals, I will use mouse neural rosettes to screen and perform functional assessments of the promising candidates. I will then perform functional studies of human neural rosettes to test our candidates, as well as previously identified regulators of asymmetric cell division. In this way, I will utilize the neural rosettes system to screen for new regulators of self-renewal and differentiation and examine the role of asymmetric cell division in human cortical development.