TY - JOUR T1 - Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0230-16.2016 SP - ENEURO.0230-16.2016 AU - Guangfan Zhang AU - William B. Titlow AU - Stephanie M. Biecker AU - Arnold J. Stromberg AU - Timothy S. McClintock Y1 - 2016/10/17 UR - http://www.eneuro.org/content/early/2016/10/17/ENEURO.0230-16.2016.abstract N2 - 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 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 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, 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.Significance Statement The nervous system develops myriad different types of neurons, many having numerous subtypes. The olfactory epithelium takes this to an extreme, with >1,000 different subtypes of olfactory sensory neuron (OSN), each defined by expression of a single odorant receptor (OR) gene. We demonstrate that Lhx2 is the homeodomain transcription factor necessary to drive expression of OR genes. By stabilizing the expression of a single OR gene and consequently triggering OSN maturation, Lhx2 drives the events that complete the process of OR gene choice, thereby defining the role of each OSN in odor detection and discrimination. ER -