Molecular events in the cell types of the olfactory epithelium during adult neurogenesis

Abstract

BackgroundAdult 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.ResultsOf 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.ConclusionsMany 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.

Activity-Dependent Genes in Mouse Olfactory Sensory Neurons

“…Differential loss of mature OSNs should preferentially affect mRNAs specific to mature OSNs, but only 4 of these mRNAs are specific to mature OSNs (S100A5, Pcp4l1, Slc17a6, Pcdh10) instead of being expressed in both mature and immature OSNs (Nickell et al 2012). This is consistent with our previous evidence that naris occlusion at the exact same age and for the same 6-day duration did not alter the number of mature OSNs and contrasts sharply with expression profiling results showing large changes in the abundance of many mature OSN mRNAs when OSN numbers decrease (Shetty et al 2005;Sammeta and McClintock 2010;Heron et al 2013). We conclude that the experimental design avoided the potential confound of loss of mature OSNs on the occluded side.…”

Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

“…9 E , F ). Macrophages respond to increased OSN turnover in order to help clear cell debris from the olfactory epithelium (Suzuki et al, 1995; Blomster et al, 2011; Heron et al, 2013). …”

“…We have previously described the use of these procedures to locate cells expressing >300 mRNAs in olfactory epithelia (Sammeta et al, 2007; Nickell et al, 2012; Heron et al, 2013). cDNA fragments of each mRNA were amplified by PCR from olfactory mucosal cDNA and cloned into pBluescript (Table 2).…”

Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

“…Several million OSNs, consisting of immature olfactory sensory neurons (iOSNs) and mature olfactory sensory neurons (mOSNs), are situated in the middle of the MOE. mOSNs are equipped with cilia, in which the olfactory cyclic adenosine monophosphate (cAMP) signaling cascade members, which are critical for proper olfactory function, are enriched (Menco, 1997; Heron et al, 2013). One unique characteristic of OSNs is their continuous neurogenesis that occurs throughout life.…”