Transcriptional changes during neuronal death and replacement in the olfactory epithelium

The olfactory epithelium has the unusual ability to replace its neurons. We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5–7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlh1, Hes6, Lmyc1, c-Myc, Mxd4, Id1, Nmyc1, Cited2, c-Myb, Mybl1, Tead2, Dp1, Gata2, Lmo1, and Sox11. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.