Royalactin induces queen differentiation in honeybees

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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.

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Figure 1: Effects of casein, 450-kDa protein, royalactin and recombinant royalactin on caste characters in the honeybee.
Figure 2: Morphological and physiological changes of Drosophila melanogaster induced by royal jelly and royalactin.
Figure 3: Morphological and physiological changes of Drosophila melanogaster induced by overexpression of royalactin.
Figure 4: Suppression of queen differentiation in honeybee with RNAi.

Change history

  • 25 May 2011

    The legend to Fig. 1 was corrected


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I thank D. Yamamoto for provision of general fruitfly treatment methods and helpful advice; and S. Hayashi and T. Adachi-Yamada for instruction of dissection techniques in Drosophila. I thank T. Nonogaki and Y. Hasada for supply of honeybee larvae; K. Yu, M. Tatar, P. Leopold, G. Korge, Y. T. Ip, T. G. Wilson and D. Yamamoto for fly stocks. We are grateful to T. Oda for the gift of royal jelly, and to W. R. S. Steele for proofreading the article.

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M.K. designed the research and performed the experiments. M.K. wrote the paper.

Correspondence to Masaki Kamakura.

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The author declares no competing financial interests.

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This file contains Supplementary Results, a Supplementary Discussion, Supplementary Methods, additional references, Supplementary Figures 1-34 with legends and Supplementary Tables 1-14. This file was replaced online on 15 October 2012 to correct Supplementary Figures 22a and 33c and again on 23 January 2013 to correct Supplementary Figure 19b.. (PDF 4372 kb)

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Kamakura, M. Royalactin induces queen differentiation in honeybees. Nature 473, 478–483 (2011) doi:10.1038/nature10093

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