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 Nhlh 1, Hes 6, Lmyc 1, c-Myc, Mxd 4, Id 1, Nmyc 1, Cited 2, c-Myb, Mybl 1, Tead 2, Dp 1, Gata 2, Lmo 1, and Sox1 1. 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.
Shetty
Ranjit S
RS
Department of Physiology, Cellular and Molecular Neuroscience of Sensory Systems Training Program, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, USA.
Bose
Soma C
SC
Nickell
Melissa D
MD
McIntyre
Jeremy C
JC
Hardin
Debra H
DH
Harris
Andrew M
AM
McClintock
Timothy S
TS
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D003714:Denervation; D020869:Gene Expression Profiling; D020868:Gene Silencing; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009831:Olfactory Mucosa / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000502:physiology*; D012333:RNA, Messenger / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger