Royalactin induces queen differentiation in honeybees

The honeybee (Apis mellifera) forms two female castes: the queen and the worker. This dimorphism depends not on genetic differences, but on ingestion of royal jelly, although the mechanism through which royal jelly regulates caste differentiation has long remained unknown. Here I show that a 57-kDa protein in royal jelly, previously designated as royalactin, induces the differentiation of honeybee larvae into queens. Royalactin increased body size and ovary development and shortened developmental time in honeybees. Surprisingly, it also showed similar effects in the fruitfly (Drosophila melanogaster). Mechanistic studies revealed that royalactin activated p70 S6 kinase, which was responsible for the increase of body size, increased the activity of mitogen-activated protein kinase, which was involved in the decreased developmental time, and increased the titre of juvenile hormone, an essential hormone for ovary development. Knockdown of epidermal growth factor receptor (Egfr) expression in the fat body of honeybees and fruitflies resulted in a defect of all phenotypes induced by royalactin, showing that Egfr mediates these actions. These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway. The difference between the queen in a honeybee colony and the workers is not a matter of genetics but of nutrition: larvae that consume royal jelly become queens. The active royal-jelly ingredient has long remained elusive, but is now identified as royalactin, a previously known protein that exhibits epidermal growth factor (EGFR)-like effects on rat hepatocytes. Surprisingly, royalactin also induces queen-like phenotypes in the fruitfly Drosophila melanogaster, increasing body size and ovary development through an EGFR-mediated signalling pathway.