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 Nhlhl, Hes6, Lmycl, c-Myc, Mxd4, Idl,Nmycl, Cited2, c-Myb, Mybll, Tead2, Dpl, Gata2, Lmol, and Soxll. 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, Lexington 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
D000344:Afferent Pathways / Q000293:injuries; D000818:Animals; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D003714:Denervation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009830:Olfactory Bulb / Q000293:injuries; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D009419:Nerve Tissue Proteins; D014157:Transcription Factors