The hallmarks of GSK-3 in morphogenesis and embryonic development metabolism in arthropods.

Several research groups around the world have studied diverse aspects of energy metabolism in arthropod disease vectors, with the aim of discovering potential control targets. As in all oviparous organisms, arthropod embryonic development is characterized by the mobilization of maternally-derived metabolites for the formation of new tissues and organs. Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase described as an important regulator of metabolism and development in a wide range of organisms. GSK-3 was first identified based on its action upon glycogen synthase, a central enzyme in glycogen biosynthesis. Currently, it is recognized as a key component of multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, cell migration, and immune response. The present review will describe the current knowledge on GSK-3 activation and its role in morphogenesis and embryonic metabolism in arthropods. Altogether, the information discussed here can spark new approaches and strategies for further studies, enhancing our understanding of these important arthropod vectors and strengthening the resources in the search for novel control methods.

Glycogen Synthase Kinase-3 is involved in glycogen metabolism control and embryogenesis of Rhodnius prolixus.

Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region. Meanwhile, the role of GSK-3 during R. prolixus embryogenesis or glycogen metabolism has not been investigated. Here we show that chemical inhibition of GSK-3 by alsterpaullone, an ATP-competitive inhibitor of GSK3, does not affect adult survival rate, though it alters oviposition and egg hatching. Specific GSK-3 gene silencing by dsRNA injection in adult females showed a similar phenotype. Furthermore, bright field and 4'-6-diamidino-2-phenylindole (DAPI) staining analysis revealed that ovaries and eggs from dsGSK-3 injected females exhibited specific morphological defects. We also demonstrate that glycogen content was inversely related to activity and transcription levels of GSK-3 during embryogenesis. Lastly, after GSK-3 knockdown, we observed changes in the expression of the Wingless (Wnt) downstream target ß-catenin as well as in members of other pathways such as the receptor Notch. Taken together, our results show that GSK-3 regulation is essential for R. prolixus oogenesis and embryogenesis.