Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

Dopamine is found in the nervous systems of both vertebrates and invertebrates. However, the specific actions of dopamine depend on the dopamine receptor type that is expressed in the target cell. As in mammals, different subtypes of dopamine receptors have been cloned and characterized from invertebrates, and these receptor subtypes have different structural and functional properties. Understanding how these receptors respond to dopamine and in which cells each receptor type is expressed is key to our understanding of the role of dopamine signaling. Comparison of the amino acid sequences and experimentally determined functional properties suggest that there are at least three distinct types of dopamine receptors in invertebrates. This review focuses on invertebrate dopamine receptors for which the genes have been isolated and identified, and examines our current knowledge of the functional and structural properties of these receptors, and their pharmacology and expression.

Honey bee queens produce a sophisticated array of chemical signals (pheromones) that influence both the behavior and physiology of their nest mates. Most striking are the effects of queen mandibular pheromone (QMP), a chemical blend that induces young workers to feed and groom the queen and primes bees to perform colony-related tasks. But how does this pheromone operate at the cellular level? This study reveals that QMP has profound effects on dopamine pathways in the brain, pathways that play a central role in behavioral regulation and motor control. In young worker bees, dopamine levels, levels of dopamine receptor gene expression, and cellular responses to this amine are all affected by QMP. We identify homovanillyl alcohol as a key contributor to these effects and provide evidence linking QMPinduced changes in the brain to changes at a behavioral level. This study offers exciting insights into the mechanisms through which QMP operates and a deeper understanding of the queen's ability to regulate the behavior of her offspring.Apis mellifera ͉ biogenic amines ͉ neuroethology ͉ neuromodulation ͉ pheromonal communication C omplex social interactions require systems of communication that are reliable and unambiguous. The honey bee, Apis mellifera, employs Ͼ50 substances to communicate with and to organize its colony, and the information that is conveyed between colony members is both subtle and sophisticated (1-3).Maintaining colony organization is a primary role of the queen, whose pheromones enable her to regulate not only the behavior but also the physiology of her nest mates. The most striking effects are those of queen mandibular pheromone (QMP), a chemical blend that induces young workers to feed and groom the queen (Fig. 1) and primes bees to perform colonyrelated tasks (4, 5). The retinue of workers that attend the queen facilitates the distribution of QMP throughout the colony, where it inhibits the rearing of new queens (6), helps prevent the development of worker ovaries (7), influences comb-building activities, (8) and affects the biosynthesis of juvenile hormone (9) [and hence the age-related behavioral ontogeny of recipient workers (10)]. Despite QMP's central role in the normal functioning and organization of honey bee colonies, very little is known about the cellular mechanisms through which it operates.We were intrigued by one of the key components of QMP, homovanillyl alcohol (HVA) (4). HVA (4-hydroxy-3-methoxyphenylethanol) bears a striking structural resemblance to dopamine (see Fig. 1 Right), a biogenic amine that plays a central role in insect behavioral regulation and motor control (11-18). The presence of this compound within the pheromone blend suggested to us that dopamine function in the brain of recipient bees might be affected by exposure to QMP. To test this hypothesis, we exposed young workers to QMP and examined its effects on brain dopamine levels, levels of dopamine receptor gene expression, and cellular responses to this amine. The results provide compelling evidence that QMP al...

The forces that orthodontic appliances apply to the teeth are transmitted through the periodontal ligament (PDL) to the supporting alveolar bone, leading to the deposition or resorption of bone, depending upon whether the tissues are exposed to a tensile or compressive mechanical strain. To evaluate the osteogenic potential of PDL cells, we applied a 12% uni-axial cyclic tensile strain to cultured human PDL cells and analyzed the differential expression of 78 genes implicated in osteoblast differentiation and bone metabolism by real-time RT-PCR array technology. Sixteen genes showed statistically significant changes in expression in response to alterations in their mechanical environment, including cell adhesion molecules and collagen fiber types. Genes linked to the osteoblast phenotype that were up-regulated included BMP2, BMP6, ALP, SOX9, MSX1, and VEGFA; those down-regulated included BMP4 and EGF. This study has expanded our knowledge of the transcriptional profile of PDL cells and identified several new mechanoresponsive genes.

SummaryThe expression of genes encoding patatin, a major tuber protein, is highly tissue-specific but is also modulated by exogenous sucrose. The patterns of transcription observed in potato plants could be due to mechanisms conferring tuber-specificity or they could reflect the concentrations of sucrose found in different tissues. To distinguish between these possibilitles, a datalled examination was made of the function of a region of the promoter previously impliceted in conferring tissue-specific and sucrose-inducible expression. Internal deletions of this region revealed three separate functional domains regulating expression. The B repeat region acted as a positive activator of transcription in the tuber and was also responsible for a degree of sucrose-inducibility. The dlatal region of the A repeat repressed transcription in leaf and tuber tissue, while the proximal region of the A repeat was able to confer sucrose-responsiveness. Each of these regions specifically bound nuclear proteins which may be putative transcription factors involved in conferring these responses. The region found to confer sucrose-inducible expression was conserved among some other genes that are also regulated by exogenous sucrose.

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BackgroundThree dopamine receptor genes have been identified that are highly conserved among arthropod species. One of these genes, referred to in honey bees as Amdop2, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. In this study we examined in parallel the functional and pharmacological properties of AmDOP2 and the honey bee octopamine receptor, AmOA1. For comparison, pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were also examined.Methodology/Principal FindingsUsing HEK293 cells heterologously expressing honey bee biogenic amine receptors, we found that activation of AmDOP2 receptors, like AmOA1 receptors, initiates a rapid increase in intracellular calcium levels. We found no evidence of calcium signaling via AmDOP1, AmDOP3 or AmTYR1 receptors. AmDOP2- and AmOA1-mediated increases in intracellular calcium were inhibited by 10 µM edelfosine indicating a requirement for phospholipase C-β activity in this signaling pathway. Edelfosine treatment had no effect on AmDOP2- or AmOA1-mediated increases in intracellular cAMP. The synthetic compounds mianserin and epinastine, like cis-(Z)-flupentixol and spiperone, were found to have significant antagonist activity on AmDOP2 receptors. All 4 compounds were effective antagonists also on AmOA1 receptors. Analysis of putative ligand binding sites offers a possible explanation for why epinastine acts as an antagonist at AmDOP2 receptors, but fails to block responses mediated via AmDOP1.Conclusions/SignificanceOur results indicate that AmDOP2, like AmOA1, is coupled not only to cAMP, but also to calcium-signalling and moreover, that the two signalling pathways are independent upstream of phospholipase C-β activity. The striking similarity between the pharmacological properties of these 2 receptors suggests an underlying conservation of structural properties related to receptor function. Taken together, these results strongly support phylogenetic analyses indicating that the AmDOP2 and AmOA1 receptor genes are immediate paralogs.

Queen mandibular pheromone (QMP) is produced by honey bee queens and used to regulate the behavior and physiology of their nestmates. QMP has recently been shown to block aversive learning in young worker bees, an effect that can be mimicked by treating bees with one of QMP's key components, homovanillyl alcohol (HVA). Although the mechanisms underlying this blockade remain unclear, HVA has been found to lower brain dopamine levels and to alter intracellular levels of cAMP in brain centers involved in learning and memory. These findings led to the hypothesis that HVA targets dopamine pathways in the brain, which are known to play a critical role in the formation of aversive olfactory memories. Here, we investigate the possibility that HVA interacts directly with dopamine receptors in the bee. We show that HVA selectively activates the D2-like dopamine receptor AmDOP3 but has neither agonist nor antagonist activity on the D1-like receptors AmDOP1 or AmDOP2 nor agonist activity on the octopamine receptor AmOA1. These results suggest a direct molecular mechanism by which queen pheromone can modulate dopamine signaling pathways. They also implicate the dopamine receptor AmDOP3 in HVA-induced blockade of aversive learning in young worker bees.