Silencing of odorant receptor gene expression by G protein M-NM-2M-NM-3 signaling ensures the expression of one odorant receptor per olfactory sensory neuron
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ABSTRACT: Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein M-NM-2M-NM-3 subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron. Total 6 samples were analyzed-3 controls & 3 samples
Project description:Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein βγ subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron.
Project description:We report RNA sequencing of single olfactory neurons from mouse olfactory epithelium in developmental progression from progenitors to precursors to immature neurons to mature neurons. Most mature neurons expressed only one of ~ 1000 odorant receptor genes (Olfrs) at high levels, whereas many immature neurons expressed low levels of multiple Olfrs. Investigating expression of odorant receptors genes in mouse olfactory sensory neurons during development.
Project description:Odorants are thought to activate sets of odorant receptors in vivo, but capturing sets of responsive receptors in vivo has never been accomplished. GeneChip microarrays were used to identify the odorant receptor mRNAs enriched in samples from activated olfactory neurons
Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in knockout mice
Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in knockout mice
Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in knockout mice
Project description:The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in knockout mice
Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. This series describes 1 of the 5 array experiments. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in conditional knockout mice