Editors' ChoiceBehavior

Tears Signal Immaturity

Science Signaling  22 Oct 2013:
Vol. 6, Issue 298, pp. ec254
DOI: 10.1126/scisignal.2004830

Chemical signals called pheromones control social behavior in mice. Ferrero et al. developed a method to screen for additional genome-encoded pheromones and identified peptides produced in an age-dependent manner. They focused on exocrine-gland secreting peptide 22 (ESP22), a peptide produced specifically in juvenile mice. The expression of Esp22 occurred in the secretory acinar cells of the tear gland and was greatest in mice between 2 and 3 weeks old. Protein analysis confirmed that ESP22 was abundant in juvenile mouse tears. Electrophysiological analysis of the vomeronasal organ (VNO), which is where mice detect pheromones, showed that recombinant ESP22 stimulated a subset of neurons. ESP22 detection depended on the channel TRPC2, which is required for VNO function. By monitoring changes in the abundance of cFos, which is increased in response to neural activity, exposure of mice to recombinant ESP22 or juvenile tears was found to stimulate neurons in the portion of the medial amygdala that projects to regions of the hypothalamus associated with defensive and reproductive responses. Wild-type male mice (C57BL/6 strain) exhibited increased mounting, a sexual behavior, of juvenile mice of the C3H strain, which lack Esp22 expression. Painting recombinant ESP22 onto C3H juvenile mice or adult wild-type females in estrous decreased sexual behavior toward these mice. Thus, ESP22 is a signal of sexual immaturity in mice that prevents precocious mating.

D. M. Ferrero, L. M. Moeller, T. Osakada, N. Horio, Q. Li, D. S. Roy, A. Cichy, M. Spehr, K. Touhara, S. D. Liberles, A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Nature 502, 368–371 (2013). [PubMed]