Fil: Choi, Jung-Mi. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Kim, Sung-Soo. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Choi, Chan-Il. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Cha, Hye Lim. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Oh, Huy-Hyen. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Oh, Huy-Hyen. Ajou University School of Medicine. The Graduate School. Department of Biomedical Sciences; Corea del Sur Fil: Ghil, Sungho. Kyonggi University. Department of Life Science; Corea del Sur Fil: Lee, Young-Don. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Lee, Young-Don. Ajou University School of Medicine. The Graduate School. Department of Biomedical Sciences; Corea del Sur Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos Fil: Suh-Kim, Haeyoung. Ajou University School of Medicine. Department of Anatomy; Corea del Sur Fil: Suh-Kim, Haeyoung. Ajou University School of Medicine. The Graduate School. Department of Biomedical Sciences; Corea del Sur Abstract: In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.