Activity plays a role in eliminating olfactory sensory neurons expressing multiple odorant receptors in the mouse septal organ

Tian, Huikai; Ma, Minghong

doi:10.1016/j.mcn.2008.04.006

Cited by 50 publications

(45 citation statements)

References 27 publications

(42 reference statements)

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“…Bottom section: Summary of the frequencies with which individual OR genes (left column) were identified from the various tissues and genotypes in scRT-PCR samples. The column to the right compares our scRT-PCR results with the frequency of expression of OR genes in sOSNs as reported in the literature, *: Tian and Ma (2008), **: Tian and Ma (2004), a : Kaluza et al (2004). IV and V refer to frequency of OR gene expression in the SO as determined by Tian and Ma (2004), IV: OR genes that were found in less than one sOSN per SO section, V: OR genes that were only identified by scRT-PCR but not confirmed by ISH on SO tissue.…”

Section: Resultsmentioning

confidence: 99%

“…Coexpression of wild-type SR1 with another OR gene has been reported in the SO of wild-type mice (Tian and Ma, 2008). SR1 is coexpressed with any of eight of the most abundant SO OR genes in 2% of sOSNs at birth.…”

Section: Normal Coexpression With Sr1mentioning

confidence: 99%

“…The cellular morphology and olfactory signal transduction of the OSNs in the SO (sOSNs) are indistinguishable from those of OSNs in the MOE (mOSNs) (Ma et al, 2003). Eight additional OR genes are expressed by another~45% of sOSNs (Tian and Ma, 2008). SR1 is further atypical as an OR, in that SR1 sOSNs and mOSNs, and heterologous cells transfected with SR1 expression constructs, respond to a wide variety of chemical ligands and over a large range of concentrations (Grosmaitre et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1

Fuss

Zhu

Mombaerts

2013

Molecular and Cellular Neuroscience

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Section: Resultsmentioning

confidence: 99%

Section: Normal Coexpression With Sr1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1

Fuss

Zhu

Mombaerts

2013

Molecular and Cellular Neuroscience

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“…Singular OR expression (a very small failure probability P fail ) is achieved by sacrificing the rate of neuronal maturation (a long time before the first activation T). Although the exact extent of singularity has not been investigated for all ∼1,400 ORs, RNA FISH in the septal organ-a small fraction of the olfactory epithelium where most neurons choose from a pool of only nine ORs-showed a 1-2% probability of expressing more than one OR in newborn mice or in sensory-deprived adults (in contrast, normal adults would have a lower failure probability of ∼0.2% due to apoptosis of neurons with more than one OR) (15).…”

Section: Resultsmentioning

confidence: 99%

Rare event of histone demethylation can initiate singular gene expression of olfactory receptors

Tan

Zong

Xie

2013

Proc. Natl. Acad. Sci. U.S.A.

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Mammals sense odors through the gene family of olfactory receptors (ORs). Despite the enormous number of OR genes (∼1,400 in mouse), each olfactory sensory neuron expresses one, and only one, of them. In neurobiology, it remains a long-standing mystery how this singularity can be achieved despite intrinsic stochasticity of gene expression. Recent experiments showed an epigenetic mechanism for maintaining singular OR expression: Once any ORs are activated, their expression inhibits further OR activation by down-regulating a histone demethylase Lsd1 (also known as Aof2 or Kdm1a), an enzyme required for the removal of the repressive histone marker H3K9me3 on OR genes. However, it remains unclear at a quantitative level how singularity can be initiated in the first place. In particular, does a simple activation/ feedback scheme suffice to generate singularity? Here we show theoretically that rare events of histone demethylation can indeed produce robust singularity by separating two timescales: slow OR activation by stepwise H3K9me3 demethylation, and fast feedback to turn off Lsd1. Given a typical 1-h response of transcriptional feedback, to achieve the observed extent of singularity (only 2% of neurons express more than one ORs), we predict that OR activation must be as slow as 5-10 d-a timescale compatible with experiments. Our model further suggests H3K9me3-to-H3K9me2 demethylation as an additional rate-limiting step responsible for OR singularity. Our conclusions may be generally applicable to other systems where monoallelic expression is desired, and provide guidelines for the design of a synthetic system of singular expression.neurogenesis | stochastic gene expression | histone modification | kinetics modeling | negative feedback I n mammals, the ability to sense odors relies on the singular expression of the olfactory receptor (OR) gene family. Despite the enormous family size (∼1,400 genes in the mouse genome), each sensory neuron only expresses one single allele of OR (1-4). It has long been thought that this singularity stems from a negative feedback in which the expression of one OR specifically silences all other ORs (5-7). However, this hypothesis has led to the question of how the one, and only one, active OR can escape its own silencing effect. In other words, it was unclear how such silencing can be biologically feasible.A series of recent studies provoked a different mechanism for OR singularity in light of epigenetic regulation. Contrary to previous belief, Magklara et al. (8) found that silencing of OR genes precedes OR expression: The histone marker H3K9me2 on OR genes become methylated into H3K9me3 as early as in the stage of neuronal progenitors, which do not yet express any ORs. H3K9me2 is a marker for localization of inactive genes into facultative heterochromatin; its further methylation into H3K9me3, however, marks OR genes for constitutive heterochromatinnuclear compartments that normally contain pericentromeric and telomeric regions. With this marker, all OR genes are deeply repressed i...

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“…Because OR-mediated negative feedback does not require G protein signaling , the exact nature of the negative feedback signal is unclear. In young animals, a small number of OSNs misexpresses multiple ORs, which however are developmentally eliminated in an activity-dependent manner (Tian and Ma 2008).…”

Section: Peripheral Olfactory Organization and Odorant Receptor Gene mentioning

confidence: 99%

Topographic Mapping--The Olfactory System

Imai¹,

Sakano²,

Vosshall³

2010

Cold Spring Harbor Perspectives in Biology

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Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils-the olfactory glomeruli-that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.T he olfactory system detects airborne organic and inorganic chemicals that originate from plant and animal metabolites and environmental and industrial sources. Odors mediate both innate and learned behaviors such as attraction and aversion, governing decisions to eat, mate, attack or flee from aggressors and predators. A remarkable feature of the olfactory system is the extraordinary diversity of possible odor molecules that exist. Although accurate measurements can be made of the detection range of visual wavelengths or auditory frequencies in humans, there are no reliable estimates of the number of odorous molecules that exist on earth or those that can be detected by a given animal species (Gilbert 2008). Nevertheless, the number of possible odorants is thought to be high, in the range of many thousands. Beyond odor detection lies the problem of odor discrimination: how can chemicals with slightly different physical properties be discriminated and associated with distinct odor percepts?Experiments investigating the molecular logic of olfaction over the last 20 years have led to major insights into how animals solve the problem of detecting and discriminating a vast number of different odor stimuli (Axel 1995). Four organizational principles have emerged from this work. First, large numbers of distinct odorant receptor (OR) genes are dedicated

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Activity plays a role in eliminating olfactory sensory neurons expressing multiple odorant receptors in the mouse septal organ

Cited by 50 publications

References 27 publications

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1

Rare event of histone demethylation can initiate singular gene expression of olfactory receptors

Topographic Mapping--The Olfactory System

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