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Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquito Aedes aegypti
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Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquito Aedes aegypti
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Journal Article
Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquito Aedes aegypti
2018
Overview
Gut microbes positively affect the physiology of many animals, but the molecular mechanisms underlying these benefits remain poorly understood. We recently reported that bacteria-induced gut hypoxia functions as a signal for growth and molting of the mosquito Aedes aegypti. In this study, we tested the hypothesis that transduction of a gut hypoxia signal requires hypoxia-induced transcription factors (HIFs). Expression studies showed that HIF-α was stabilized in larvae containing bacteria that induce gut hypoxia but was destabilized in larvae that exhibit normoxia. However, we could rescue growth of larvae exhibiting gut normoxia by treating them with a prolyl hydroxylase inhibitor, FG-4592, that stabilized HIF-α, and inhibit growth of larvae exhibiting gut hypoxia by treating them with an inhibitor, PX-478, that destabilized HIF-α. Using these tools, we determined that HIF signaling activated the insulin/insulin growth factor pathway plus select mitogen-activated kinases and inhibited the adenosine monophosphate-activated protein kinase pathway. HIF signaling was also required for growth of the larval midgut and storage of neutral lipids by the fat body. Altogether, our results indicate that gut hypoxia and HIF signaling activate multiple processes in A. aegypti larvae, with conserved functions in growth and metabolism.
Publisher
National Academy of Sciences
Subject
/ Aedes - growth & development
/ AMP-Activated Protein Kinases - genetics
/ AMP-Activated Protein Kinases - metabolism
/ Animals
/ Aryl Hydrocarbon Receptor Nuclear Translocator - genetics
/ Aryl Hydrocarbon Receptor Nuclear Translocator - metabolism
/ Bacteria
/ Fat body
/ Fat Body - growth & development
/ Female
/ Hypoxia
/ Hypoxia-Inducible Factor 1, alpha Subunit - genetics
/ Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
/ Insect Proteins - metabolism
/ Insulin
/ Kinases
/ Larva - growth & development
/ Larvae
/ Lipids
/ Male
/ Midgut
/ Molting
