Expression of Nonclassical Class I Major Histocompatibility Genes Defines a Tripartite Organization of the Mouse Vomeronasal System

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Abstract
The epithelium of the mouse vomeronasal organ (VNO) consists of apical and basal layers of neuronal cell bodies. Vomeronasal sensory neurons (VSNs) with cell bodies in the basal layer express the G-protein subunitGαoand members of the V2R superfamily of vomeronasal receptor genes and project their axons to the posterior accessory bulb (AOB).V2R+VSNs also express particular patterns of a family of nine nonclassical class I major histocompatibilityMhcgenes, theH2-Mvgenes. The function of H2-Mv molecules remains unknown. H2-Mv molecules have been reported to be associated with V2R molecules and have been proposed to participate in pheromone detection. Here, we find that a substantial fraction ofV2R+VSNs does not express these nineH2-Mvgenes. The cell bodies ofH2-Mv+andH2-Mv−VSNs reside in the lower and upper sublayers of the basal layer, respectively. This spatial segregation is maintained at the level of the AOB:H2-Mv+andH2-Mv−VSNs project their axons to the posterior and anterior subdomains of the posterior AOB, respectively. By generating a C-terminal green fluorescent protein fusion protein with M10.2 in gene-targeted mice, we observe subcellular localization of M10.2 not only in dendrites but also in axons of VSNs. Our results reveal a tripartite organization of the VNO and AOB, question the generality of the requirement of these nine H2-Mv molecules for V2R surface expression, and suggest that H2-Mvs can function in both dendrites and axons.