Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

A developmental program of epigenetic repression prepares each mammalian olfactory sensory neuron (OSN) to strongly express one allele from just one of hundreds of odorant receptor (OR) genes, but what completes this process of OR gene choice by driving the expression of this allele is incompletely...

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Bibliographic Details
Published in:eNeuro 2016-09, Vol.3 (5), p.ENEURO.0230-16.2016
Main Authors: Zhang, Guangfan, Titlow, William B, Biecker, Stephanie M, Stromberg, Arnold J, McClintock, Timothy S
Format: Article
Language:English
Subjects:
Animals
Female
Fluorescent Antibody Technique
Gene Expression Regulation - physiology
Homeodomain Proteins - metabolism
In Situ Hybridization
LIM-Homeodomain Proteins - genetics
LIM-Homeodomain Proteins - metabolism
Male
Mice, Transgenic
Microarray Analysis
Mutation
New Research
Olfactory Receptor Neurons - cytology
Olfactory Receptor Neurons - metabolism
Receptors, Odorant - metabolism
RNA, Messenger - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary:A developmental program of epigenetic repression prepares each mammalian olfactory sensory neuron (OSN) to strongly express one allele from just one of hundreds of odorant receptor (OR) genes, but what completes this process of OR gene choice by driving the expression of this allele is incompletely understood. Conditional deletion experiments in mice demonstrate that Lhx2 is necessary for normal expression frequencies of nearly all ORs and all trace amine-associated receptors, irrespective of whether the deletion of is initiated in immature or mature OSNs. Given previous evidence that Lhx2 binds OR gene control elements, these findings indicate that Lhx2 is directly involved in driving OR expression. The data also support the conclusion that OR expression is necessary to allow immature OSNs to complete differentiation and become mature. In contrast to the robust effects of conditional deletion of , the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects on expression that reveal independent effects of these two transcription factors. While Lhx2 is necessary for OR expression that supports OR gene choice, Emx2 can act differently; perhaps by helping to control the availability of OR genes for expression.
ISSN:2373-2822
2373-2822
DOI:10.1523/eneuro.0230-16.2016