Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis.
The 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.
Hudson
Chantelle D
CD
Medical Molecular Biology Unit, Institute of Child Health, London, United Kingdom.
Podesta
Jennifer
J
Henderson
Deborah
D
Latchman
D S
DS
Budhram-Mahadeo
V
V
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004268:DNA-Binding Proteins; C494189:Pou4f1 protein, mouse; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53