We tested the hypothesis that queen mandibular pheromone (QMP) causes changes in gene expression in the brain of the adult worker honey bee, and that these changes can be correlated to the downstream behavioral responses induced by QMP. In support of the first hypothesis, cage experiments revealed that QMP transiently regulated expression of several hundred genes and chronically regulated the expression of 19 genes. Several of these genes were also affected by QMP in experiments with bee colonies in the field, demonstrating robust gene regulation by pheromone. To evaluate the second hypothesis, we focused on one function of QMP: delaying the transition from working in the hive (e.g., brood care, or ''nursing'') to foraging. We compared the list of QMPregulated genes with the lists of genes differentially regulated in nurse and forager brains generated in a separate study. QMP consistently activated ''nursing genes'' and repressed ''foraging genes,'' suggesting that QMP may delay behavioral maturation by regulating genes in the brain that produce these behavioral states. We also report here on an ortholog of the Drosophila transcription factor kruppel homolog 1 that was strongly regulated by QMP, especially in the mushroom bodies of the bee brain. These results demonstrate chronic gene regulation by a primer pheromone and illustrate the potential of genomics to trace the actions of a pheromone from perception to action, and thereby provide insights into how pheromones regulate social life.
Many animal species, from insects to mammals, communicate via pheromones, chemicals that cause dramatic alterations in physiology and behavior. The recent identification of olfactory and pheromone receptors in Drosophila melanogaster and the mouse have provided new insights into how the olfactory system senses and encodes odorants (reviewed in refs. 1 and 2). It also has been demonstrated that pheromones affect gene expression in brain neurons, particularly with respect to immediate-early genes (3, 4). However, the molecular mechanisms by which pheromones are further transduced in the brain to influence behavior are only beginning to be understood (1). Particularly interesting are long-term changes in brain gene expression that might result from exposure to primer pheromones. These long-term changes in gene expression may be responsible for inducing long-term changes in physiology and behavior, a hallmark of primer pheromone action. Here we report on our efforts to use the honey bee (Apis mellifera) to study the effects of a primer pheromone on brain gene expression. We also have begun to correlate these gene expression changes with pheromone-mediated behavioral changes.Honey bees show complex social organization that is controlled to a large extent by pheromones, many of which have been well characterized, both chemically and with respect to their specific behavioral effects (5-8). We studied the best understood bee pheromone, queen mandibular pheromone (QMP), a wellcharacterized blend that is part of a recently identified nin...