The Vomeronasal Organ Mediates Interspecies Defensive Behaviors through Detection of Protein Pheromone Homologs

SummaryPotential predators emit uncharacterized chemosignals that warn receiving species of danger. Neurons that sense these stimuli remain unknown. Here we show that detection and processing of fear-evoking odors emitted from cat, rat, and snake require the function of sensory neurons in the vomeronasal organ. To investigate the molecular nature of the sensory cues emitted by predators, we isolated the salient ligands from two species using a combination of innate behavioral assays in naive receiving animals, calcium imaging, and c-Fos induction. Surprisingly, the defensive behavior-promoting activity released by other animals is encoded by species-specific ligands belonging to the major urinary protein (Mup) family, homologs of aggression-promoting mouse pheromones. We show that recombinant Mup proteins are sufficient to activate sensory neurons and initiate defensive behavior similarly to native odors. This co-option of existing sensory mechanisms provides a molecular solution to the difficult problem of evolving a variety of species-specific molecular detectors.PaperFlick To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (35605 K)

Graphical AbstractFigure optionsDownload high-quality image (391 K)Download as PowerPoint slideHighlights
► Mice display innate fear-like behavior to diverse predator odors
► Mup proteins purified from cats and rats are sufficient to evoke this behavior
► Vomeronasal sensory neurons are necessary for both detection and response
► Predator Mups and mouse Mup pheromones activate different subsets of neurons