Lhx2 determines odorant receptor expression frequency in mature olfactory sensory neurons

Guangfan Zhang, William B. Titlow, Stephanie M. Biecker, Arnold J. Stromberg, Timothy S. McClintock

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 Lhx2 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 Lhx2, the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects on Olfr15 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.

Original languageEnglish
Article numbere0230-16.2016
JournaleNeuro
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Zhang et al.

Funding

This research was supported by National Institutes of HealthNIH Grants R01-DC-007194, R01-DC-002736, K18-DC-013343, and R21-DC-014468 to T.S.M.; and UL1-TR-001998 and 5P20-GM-103436-15 to A.J.S. Received August 7, 2016; accepted October 10, 2016; First published October 17, 2016. The authors declare no competing financial interests. Author contributions: T.S.M. designed research; G.Z., W.B.T., S.M.B., and T.S.M. performed research; A.J.S. and T.S.M. analyzed data; T.S.M. wrote the paper. This research was supported by National Institutes of Health Grants R01-DC-007194, R01-DC-002736, K18-DC-013343, and R21-DC-014468 to T.S.M.; and UL1-TR-001998 and 5P20-GM-103436-15 to A.J.S.

FundersFunder number
National Institutes of HealthNIH
National Institutes of Health (NIH)R21-DC-014468, 5P20-GM-103436-15, K18-DC-013343, R01-DC-007194, UL1-TR-001998
National Institute on Deafness and Other Communication DisordersR01DC002736

    Keywords

    • Enhancer
    • Gene expression
    • Olfaction
    • Promoter
    • Smell
    • Transcription

    ASJC Scopus subject areas

    • General Neuroscience

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