Molecular Evidence for a Functional Ecdysone Signaling System in Brugia malayi

Filarial parasites such as Brugia malayi and Onchocerca volvulus are the causative agents of the tropical diseases lymphatic filariasis and onchocerciasis, which infect 150 million people, mainly in Africa and Southeast Asia. Filarial nematodes have a complex life cycle that involves transmission and development within both mammalian and insect hosts. The successful completion of the life cycle includes four molts, two of which are triggered upon transmission from one host to the other, human and mosquito, respectively. Elucidation of the molecular mechanisms involved in the molting processes in filarial nematodes may yield a new set of targets for drug intervention. In insects and other arthropods molting transitions are regulated by the steroid hormone ecdysone that interacts with a specialized hormone receptor composed of two different proteins belonging to the family of nuclear receptors. We have cloned from B. malayi two members of the nuclear receptor family that show many sequence and biochemical properties consistent with the ecdysone receptor of insects. This finding represents the first report of a functional ecdysone receptor homolog in nematodes. We have also established a transgenic hormone induction assay in B. malayi that can be used to discover ecdysone responsive genes and potentially lead to screening assays for active compounds for pharmaceutical development

PDK1 and HR46 Gene Homologs Tie Social Behavior to Ovary Signals

The genetic basis of division of labor in social insects is a central question in evolutionary and behavioral biology. The honey bee is a model for studying evolutionary behavioral genetics because of its well characterized age-correlated division of labor. After an initial period of within-nest tasks, 2–3 week-old worker bees begin foraging outside the nest. Individuals often specialize by biasing their foraging efforts toward collecting pollen or nectar. Efforts to explain the origins of foraging specialization suggest that division of labor between nectar and pollen foraging specialists is influenced by genes with effects on reproductive physiology. Quantitative trait loci (QTL) mapping of foraging behavior also reveals candidate genes for reproductive traits. Here, we address the linkage of reproductive anatomy to behavior, using backcross QTL analysis, behavioral and anatomical phenotyping, candidate gene expression studies, and backcross confirmation of gene-to-anatomical trait associations. Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the nectar and pollen foraging bias of workers. These findings implicate two genes that were not known previously to influence complex social behavior. Also, they outline how selection may have acted on gene networks that affect reproductive resource allocation and behavior to facilitate the evolution of social foraging in honey bees

AHR38, a homolog of NGFI–B, inhibits formation of the functional ecdysteroid receptor in the mosquito Aedes aegypti

In anautogenous mosquitoes, vitellogenesis, the key event in egg maturation, requires a blood meal. Consequently, mosquitoes are vectors of numerous devastating human diseases. After ingestion of blood, 20–hydroxyecdysone activates yolk protein precursor (YPP) genes in the metabolic tissue, the fat body. An important adaptation for anautogenicity is the previtellogenic developmental arrest (the state-of-arrest) preventing the activation of YPP genes in previtellogenic females prior to blood feeding. Here, we show that a retinoid X receptor homolog, Ultraspiracle (AaUSP), which is an obligatory partner in the functional ecdysteroid receptor, exists at the state-of-arrest as a heterodimer with the orphan nuclear receptor AHR38, a homolog of Drosophila DHR38 and nerve growth factor-induced protein B. Yeast two-hybrid and glutathione S-transferase pull-down assays demonstrate that AHR38 can interact strongly with AaUSP. AHR38 also disrupts binding of ecdysteroid receptor to ecdysone response elements. Cell co-transfection of AHR38 with AaEcR and AaUSP inhibits ecdysone-dependent activation of a reporter gene by the ecdysteroid receptor. Co-immunoprecipitation experiments indicate that AaUSP protein associates with AHR38 instead of AaEcR in fat body nuclei at the state-of-arrest