Down syndrome cell adhesion molecule (Dscam) is essential for self-avoidance and tiling of dendritic development in sensory neurons in Drosophila. Recent studies also show that DSCAM together with its closely related protein DSCAML1 functions in dendritic self-avoidance of a certain types of interneuron in mammalian retina. However, the functions of these DSCAMs in developing mammalian cerebral cortex are not well understood. Here we reduced the expression of DSCAM or DSCAML1 in mouse cortical neurons by RNA interference both in vitro and in vivo. We found that knockdown of DSCAM or DSCAML1 increases the complexity of proximal dendritic branching, and impedes the axon growth in cultured neurons. In vivo knockdown experiments showed that both DSCAM and DSCAML1 contribute to normal radial migration and callosal projection during the postnatal development. Our results indicate an important role of DSCAM and DSCAML1 in the development of cortical neural network.