Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression.

The accessory olfactory system controls social and sexual interactions in mice that are crucial for survival. Vomeronasal sensory neurons (VSNs) form synapses with dendrites of second order neurons in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor coalesce into multiple glomeruli within spatially conserved regions of the AOB. Here we examine the role of the Kirrel family of transmembrane proteins in the coalescence of VSN axons within the AOB. We find that Kirrel2 and Kirrel3 are differentially expressed in subpopulations of VSNs and that their expression is regulated by activity. Although Kirrel3 expression is not required for early axonal guidance events, such as fasciculation of the vomeronasal tract and segregation of apical and basal VSN axons in the AOB, it is necessary for proper coalescence of axons into glomeruli. Ablation of Kirrel3 expression results in disorganization of the glomerular layer of the posterior AOB and formation of fewer, larger glomeruli. Furthermore, Kirrel3(-/-) mice display a loss of male-male aggression in a resident-intruder assay. Taken together, our results indicate that differential expression of Kirrels on vomeronasal axons generates a molecular code that dictates their proper coalescence into glomeruli within the AOB.