Royalactin induces queen differentiation in honeybees. Biotechnology Research Center. Nature

Biotechnology Research Center, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan.
Nature (Impact Factor: 41.46). 05/2011; 473(7348):478-83. DOI: 10.1038/nature10093
Source: PubMed

ABSTRACT 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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    • "In many species, a eusocial colony is composed of one queen and largely non-reproductive workers that are the queen's offspring (Wilson, 1971, Michener, 1974). Whether a queen's offspring becomes a worker or a future queen is often mediated by the queen herself: for example, (1) the queen in some social wasps and bees maintains the reproductive monopoly of the colony through aggression (Fletcher and Ross, 1985); (2) in many social insects the queen can feed offspring with food of different quantity or quality influencing offspring's future reproductive caste (i.e., queen or worker) (e.g., O'Donnell, 1998, Bourke and Ratnieks, 1999, Kapheim et al., 2011, Brand and Chapuisat, 2012); (3) in an ant species the queen can deposit hormones in the eggs inducing offspring to develop into workers (Schwander et al., 2008); (4) in certain wasp and termite species the queen can produce pheromones that prevent offspring from becoming queens (Bhadra et al., 2010, Matsuura et al., 2010); and (5) in honeybees queen pheromones can induce workers to feed larvae without royal jelly causing larvae to develop into workers (Le Conte and Hefetz, 2008, Kamakura, 2011). In addition to influencing caste determination, queens can use pheromones to keep workers' ovaries undeveloped (e.g., Holman et al., 2010, Van Oystaeyen et al., 2014), and to alter workers' brain functioning inducing workers to perform various tasks (Beggs et al., 2007). "
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    ABSTRACT: Inmany eusocial species, queens use pheromones to influence offspring to express worker phenotypes. While evidence suggests that queen pheromones are honest signals of the queen's reproductive health, here I show that queen's honest signaling can result fromancestralmaternalmanipulation. I develop amathematicalmodel to study the coevolution of maternalmanipulation, offspring resistance tomanipulation, andmaternal resource allocation. I assume that (1) maternalmanipulation causes offspring to be workers against offspring's interests; (2) offspring can resist at no direct cost, as is thought to be the case with pheromonalmanipulation; and (3) themother chooses how much resource to allocate to fertility andmaternal care. In the coevolution of these traits, I find thatmaternal care decreases, thereby increasing the benefit that offspring obtain fromhelp, which in the long run eliminates selection for resistance. Consequently, ancestralmaternalmanipulation yields stable eusociality despite costless resistance. Additionally, ancestralmanipulation in the long run becomes honest signaling that induces offspring to help. These results indicate that both eusociality and its commonly associated queen honest signaling can be likely to originate fromancestralmanipulation This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Evolutionary Biology 09/2015; DOI:10.1111/jeb.12744 · 3.23 Impact Factor
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    • "Bisulfite mapping, sequencing and expression analyses. DNA was treated with sodium bisulfite and primers (Supplementary Table 1) were designed for converted products of the 5 0 region (based on Kamakura, 2011) of C. floridanus Egfr (scaffold 550: bp113394-bp113619; located using GBrowse of the Hymenoptera Genome "
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    ABSTRACT: Complex quantitative traits, like size and behaviour, are a pervasive feature of natural populations. Quantitative trait variation is the product of both genetic and environmental factors, yet little is known about the mechanisms through which their interaction generates this variation. Epigenetic processes, such as DNA methylation, can mediate gene-by-environment interactions during development to generate discrete phenotypic variation. We therefore investigated the developmental role of DNA methylation in generating continuous size variation of workers in an ant colony, a key trait associated with division of labour. Here we show that, in the carpenter ant Camponotus floridanus, global (genome-wide) DNA methylation indirectly regulates quantitative methylation of the conserved cell-signalling gene Epidermal growth factor receptor to generate continuous size variation of workers. DNA methylation can therefore generate quantitative variation in a complex trait by quantitatively regulating the transcription of a gene. This mechanism, alongside genetic variation, may determine the phenotypic possibilities of loci for generating quantitative trait variation in natural populations.
    Nature Communications 04/2015; 6. DOI:10.1038/ncomms7513 · 11.47 Impact Factor
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    • "This molecular cascade is best resolved for the honeybee Apis mellifera, where development of the queen caste is induced by feeding larvae with " royal jelly " , a special glandular secretion produced by worker bees. Components of this secretion, including Royalactin, Major Royal Jelly proteins, and a fatty acid Histone Deacetylase inhibitor , likely activate epidermal growth factor receptor (EGFR) signaling in the larval fat body (Kamakura 2011), which in turn activates downstream pathways that directly or indirectly affect developmental trajectories (e.g., insulin-like signaling, PI3K/TOR/S6K, Ras/Raf/MAPK; Patel et al. 2007; Kamakura 2011; Mutti et al. 2011; Wolschin et al. 2011; Badisco et al. 2013). Experimental gene knock-downs, as well as comparative transcriptome and methylome studies, performed mostly in honeybees, have revealed extensive caste-dependent changes in gene expression and epigenetic regulation (Kucharski et al. 2008; Elango et al. 2009; Bonasio et al. 2012; Shi et al. 2012; Simola, Ye, et al. 2013) for a wide range of genes, for example, hexamerins (Hoffman and Goodisman 2007; Hunt et al. 2007; Cameron et al. 2013), "
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    ABSTRACT: Developmental plasticity allows for the remarkable morphological specialization of individuals into castes in eusocial species of Hymenoptera. Developmental trajectories that lead to alternative caste fates are typically determined by specific environmental stimuli that induce larvae to express and maintain distinct gene expression patterns. While most eusocial species express two castes, queens and workers, the ant Cardiocondyla obscurior expresses diphenic females and males; this provides a unique system with four discrete phenotypes to study the genomic basis of developmental plasticity in ants. We sequenced and analyzed the transcriptomes of 28 individual C. obscurior larvae of known developmental trajectory, providing the first in-depth analysis of gene expression in eusocial insect larvae. Clustering and transcription factor binding site analyses revealed that different transcription factors and functionally distinct sets of genes are recruited during larval development to induce the four alternative trajectories. In particular, we found complex patterns of gene regulation pertaining to sphingolipid metabolism, a conserved molecular pathway involved in development, obesity and aging. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail:
    Molecular Biology and Evolution 02/2015; 32(6). DOI:10.1093/molbev/msv039 · 9.11 Impact Factor
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