The proteins encoded by the p53 and Nf1 tumor suppressor genes are involved in cell signaling and regulation of proliferation during normal development and differentiation, as well as during tumor progression. To characterize the roles of these genes in the proliferation and survival of embryonic neurons, we have used dissociated cultures of sympathetic superior cervical ganglia (SCG) isolated from p53 and Nf1 single and compound-mutant mouse embryos. We have defined a temporal window for p53 involvement in sympathetic neuron survival and proliferation. Moreover, our results indicate that cooperativity between mutations in Nf1 and p53 prolongs SCG neuron proliferation and increases the incidence of neural tube defects in compound-mutant embryos.