BACKGROUND: Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium.
RESULTS: Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs.
CONCLUSIONS: Many of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns were consistent with the transition into a neuronal morphology (neuritogenesis) and later patterns with neuronal homeostasis. Overall, gene expression patterns during adult olfactory neurogenesis showed substantial similarity to those of embryonic brain.
Digital Object Identifier (DOI)
Funded by R01 DC007194 and R21 DC009624 to T.Mc., F32 DC011427 to P.M.H. and UL1TR000117 to A.J.S.
This database was compiled from this article and two other articles.
Heron, Paula M.; Stromberg, Arnold J.; Breheny, Patrick; and McClintock, Timothy S., "Molecular Events in the Cell Types of the Olfactory Epithelium during Adult Neurogenesis" (2013). Physiology Faculty Publications. 18.
Additional file 1: Table S1: Significant mRNAs; Up list followed by Down list
1756-6606-6-49-s2.pdf (2544 kB)
Additional file 2: Transcripts that increased after bulbectomy even though their P(sp) mature OSN values predict expression in mature OSNs proved to be expressed in non-OSN cell types
1756-6606-6-49-s3.pdf (5574 kB)
Additional file 3: Examples of mature OSN expression patterns of transcripts that went down after bulbectomy
1756-6606-6-49-s4.pdf (1858 kB)
Additional file 4: Transcripts that decreased after bulbectomy even though their P(sp) Other values predict expression in non-OSN cell types proved to be expressed in OSNs
1756-6606-6-49-s5.xls (64 kB)
Additional file 5: Differentially abundant transcription factor mRNAs
1756-6606-6-49-s6.xlsx (39 kB)
Additional file 6: DNA fragments used for in situ hybridization probes