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 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 ofLhx2is 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 ofLhx2, the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects onOlfr15expression 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.
Department of Physiology, University of Kentucky , Lexington, Kentucky 40536-0298.
Guangfan
G
Zhang
Department of Physiology, University of Kentucky , Lexington, Kentucky 40536-0298.
William B
WB
Titlow
Department of Physiology, University of Kentucky , Lexington, Kentucky 40536-0298.
Stephanie M
SM
Biecker
Department of Statistics, University of Kentucky , Lexington, Kentucky 40536-0082.
Arnold J
AJ
Stromberg
Department of Physiology, University of Kentucky , Lexington, Kentucky 40536-0298.
Timothy S
0000-0002-4243-5323
TS
McClintock
D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009154:Mutation; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018035:Receptors, Odorant / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099260:Empty Spiracles Homeobox Proteins
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D018035:Receptors, Odorant; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C489784:Lhx2 protein, mouse
enhancer; gene expression; olfaction; promoter; smell; transcription