The importance of lateral inhibition mediated by NOTCH signaling is well demonstrated to control neurogenesis both in invertebrates and vertebrates. We have identified the chicken homolog of Drosophila numb, which suppresses NOTCH signaling. We show that chicken NUMB (c-NUMB) protein is localized to the basal cortex of mitotic neuroepithelial cells, suggesting that c-NUMB regulates neurogenesis by the modification of NOTCH signaling through asymmetrical cell division. Consistent with this suggestion, we show (1) that c-NUMB interferes with the nuclear translocation of activated c-NOTCH-1 through direct binding to the PEST sequence in the cytoplasmic domain of c-NOTCH-1 and (2) that c-NUMB interferes with c-NOTCH-1-mediated inhibition of neuronal differentiation.