Targeting the Reproductive Capacity of the World’s Most Dangerous Animal: The Mosquito.
Mosquitoes thrive in surprising places. They make their homes in the stagnant waters that collect in tire stacks at auto body shops1 or between the train tracks in the London Underground2 and, against all odds, flourish. This ability to successfully adapt to seemingly hostile environmental conditions allows mosquitoes to invade expansive geographic regions—in part because of this, mosquitoes have emerged as the world’s foremost killers of humans. Currently, researchers are focused on developing a deeper understanding of the behavioral and physiological adaptations that allow mosquitoes to succeed in such unfavorable conditions, and how we might harness this knowledge to combat deadly mosquito-borne diseases. Research to identify new mosquito control strategies is essential, because climate change modeling currently predicts that approximately half of the world’s population will be at risk of mosquito-borne virus transmission by 20503.
As members of the Duvall Lab in the Columbia University Department of Biological Sciences, our research is focused on elucidating the molecular mechanisms underlying a variety of mosquito behaviors, including host-seeking, blood-feeding, and mating. One of the mosquito species that we house here in the Duvall Lab is the Asian Tiger mosquito, Aedes albopictus. This mosquito is a preeminent public health concern because it carries and transmits pathogens that cause deadly diseases including chikungunya, dengue and dirofilariasis. Pathogen transmission occurs when female mosquitoes bite and blood feed on vertebrate hosts.
Aedes albopictus are uniquely dangerous to public health due to their successful invasion across diverse environments, attributed to their ability to produce what are known as diapause eggs. Diapause, a state of preprogrammed developmental arrest that is usually initiated in response to unfavorable environmental conditions, is a process found in different forms across many species. One such species is Caenorhabditis elegans, or C. elegans, which enters diapause when larvae experience starvation, overcrowding, and/or higher temperatures. In many mammalian species, embryos enter diapause in utero when resources are limited, and do not complete development until the likelihood of survival increases4. In other animals, diapause is actually induced in developing embryos by the mother, a phenomenon known as maternally-instigated diapause. In Ae. albopictus, diapause in embryos is induced by the mother mosquito carrying eggs, but unlike in some mammalian species, the adult mosquito does not actually survive to see her eggs hatch. Instead, female mosquitoes lay diapause eggs that (1) are in a state of developmental arrest and (2) are equipped to resist desiccation, so they can survive the winter season until conditions favor hatching in the spring. The eggs’ ability to survive the winter makes Ae. albopictus able to thrive in surprisingly harsh conditions across a wide geographic range.
Diapause induction occurs when Ae. albopictus detect “fall” conditions, or environmental conditions that convey the changing of seasons and the nearing of winter. The mechanisms responsible for detecting “fall” conditions, and subsequently priming the female mosquito to provision her eggs to survive the winter are not fully understood. It is known that while egg development is not completed until the adult female mosquito obtains a blood meal, the diapause fate of her embryos may be determined by the environmental conditions she experienced during pupal development, long before the mosquito is mature enough to blood feed, or have her eggs fertilized by a male. Field studies have yielded exciting patterns between mosquito populations across the globe that experience varied seasonal conditions and the behaviors associated with laying diapause eggs. However, many questions remain unanswered.
Researchers studying embryonic diapause in Ae. albopictus have therefore established the conditions necessary to induce diapause in laboratory conditions. “Fall” conditions rely on a combination of reduced temperature and day length. Day length is especially important, because it is a more reliable indicator of the upcoming winter season than temperature alone. Those of us who live in New York City have become accustomed to the unseasonably warm fall weather. One can imagine that if a female mosquito were to experience a warm fall day and interpret the conditions as favorable, she would produce eggs that are not in a state of developmental arrest, and her eggs would die when temperatures eventually drop.
Dr. In Hae Lee, a postdoctoral fellow in the Duvall Lab, has led the effort to establish reliable “spring” and “fall” conditions in order to equip the lab to conduct diapause experiments. Part of the newly established lab space, described in PhD student Paige Wilson’s recent newsletter article, includes environmental rooms and incubators where we have precise control over day length, temperature, and humidity. The conditions have been calibrated to consistently induce the production of diapause eggs in animals housed in the “fall”-condition incubators, and non-diapause eggs in animals housed in “spring”-condition incubators. Establishing conditions that reliably induce (or do not induce) maternally-instigated diapause has allowed us to start asking questions about the mechanisms responsible for diapause. Dr. Lee’s project, for example, sets out to analyze the neural mechanisms involved in detecting environmental conditions, and subsequently communicating the necessary signals to undergo a reproductive switch and properly prime ovaries to create diapause eggs.
Understanding the neural pathways that induce maternally-instigated diapause in Ae. albopictus will open the door to manipulating the mosquito’s reproductive capacity and therefore its vectorial efficacy. The work that Dr. In Hae Lee and others are conducting in the Duvall Lab will help us learn exactly what makes these animals capable of such dangerous adaptability. This research will be critical for identifying new targets for tools designed to curb mosquito-borne disease, which is particularly pressing as climate change continues to enable the rapid expansion of mosquito habitats around the world.
1. Lee IH, Duvall LB. Maternally Instigated Diapause in Aedes albopictus: Coordinating Experience and Internal State for Survival in Variable Environments. Front Behav Neurosci. 2022;16:778264. doi:10.3389/fnbeh.2022.778264
2. Byrne K, Nichols RA. Culex pipiens in London Underground tunnels: differentiation between surface and subterranean populations. Heredity (Edinb). Jan 1999;82 ( Pt 1):7-15. doi:10.1038/sj.hdy.6884120
3. Kraemer MUG, Reiner RC, Brady OJ, et al. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus. Nat Microbiol. May 2019;4(5):854-863. doi:10.1038/s41564-019-0376-y
4. Miller DL, Roth MB. C. elegans are protected from lethal hypoxia by an embryonic diapause. Curr Biol. Jul 28 2009;19(14):1233-7. doi:10.1016/j.cub.2009.05.066