AbstractThe Brn‐3a transcription factor is critical for survival and differentiation of sensory neurons derived from neural crest cells (NCC). Interaction of Brn‐3a with p53 results in differential effects on target gene expression, which profoundly affects fate of neuronal cells. Here we demonstrate colocalization of p53 in a subset of Brn‐3a‐positive NCC‐derived cells fated for the sensory neuronal lineage. The distinct morphology of Brn‐3a/p53‐coexpressing cells suggested a differentiated neuronal cell type, and this was confirmed by colocalization of p53 with differentiation marker NF‐160. Functional effects of Brn‐3a/p53 coexpression were analyzed in NCC cultured from Brn‐3a −/− embryos, which showed significantly increased apoptosis upon induction of p53 compared with wild‐type NCC, suggesting that Brn‐3a modulates the p53‐mediated fate of NCC that coexpress both factors. Thus, p53 is expressed in neuronal cells undergoing differentiation as well as apoptosis. Interaction with Brn‐3a in sensory neurons may be critical for modulating p53‐mediated gene expression and hence cell fate. © 2004 Wiley‐Liss, Inc.