Pattern of expression of the Jun family of transcription factors during the early development of the inner ear: implications in apoptosis

Jun transcription factors have been implicated in the regulation of cell pr oliferation, differentiation and apoptosis, We have investigated the relati onship between Jun expression and cell death in the developing chicken inne r ear. c-jun and junD transcripts were expressed in the epithelium of the o tic placode and otic vesicle. c-jun expression was restricted to the dorsal area of the otic pit (stages 14-17), dorsal otic vesicle and cochleo-vesti bular ganglion (stages 18-20), junD expression was transient and occurred i n the dorsal and upper medial aspects of the otic pit and otic cup, but it was down-regulated in the otic vesicle, A parallel TUNEL analysis revealed that expression of c-jun co-located within areas of intense apoptosis, Furt hermore, phosphorylation of c-Jun at serine-63 by Jun amino-terminal-kinase s was detected in the dorsal otic pit, otic vesicle and cochleo-vestibular ganglion. c-Jun protein exhibited DNA binding activity, as assessed by gel mobility shift assays. The association between c-Jun and apoptosis was furt her demonstrated by studying nerve growth factor-induced apoptosis in cultu red otic vesicles. Nerve growth factor-induced cell death and c-Jun phospho rylation that were suppressed by insulin-like growth factor-I and by viral- mediated overexpression of Raf, which had survival effects. In conclusion, the precise regulation of the expression and activity of Jun proteins in th e otic primordium suggests that it may operate as a fundamental mechanism d uring organogenesis.