Mosquitoes are the deadliest animals in the world, causing nearly 1 million human deaths a year. Two species are chiefly responsible for this mortality: Anopheles gambiae, which transmit malaria in tropical climates, and Aedes aegypti, found in cooler, urbanized environments where they transmit dengue, yellow fever, zika, and other viruses.

In an inspired project in the MBL Neurobiology course, faculty and students set out to create a catalog or “atlas” of the cells in the nervous system of Aedes larvae. They focused on the ventral nerve cord, a central hub for controlling mosquito behavior, physiology and development. The first of multiple papers from this effort was published recently in Neural Development.

Mosquitoes transmit their pathogens while taking a blood meal from a human or other animal, so the behavior and physiology of adult mosquitoes have been intensively studied. However, the Neurobiology team focused on the larvae, since events during larval development shape adult traits. They found much of interest.

“We found particular populations of neurons that likely regulate developmental timing and progression from the larval state to the pupal state to adult. So, it seems plausible if you could target those neurons, you could basically kill the larvae. This might be an avenue to a larvicide,” said senior author Jay Z. Parrish of University of Washington, a Neurobiology course faculty member since 2012.

They also discovered a larval neural circuit that “gives mosquitoes the sense of being sated. It regulates the size of the blood meal and how much they want to eat. It would be interesting to know how modulating those circuits might affect feeding behavior [in the adult],” Parrish said.

A fortunate re-direction

The research, which spread over several summers in the course, arose as “one of those funny things that happens during the summer in Woods Hole,” Parrish said. One of the course faculty had brought in some mosquitoes to look at how they respond to temperature, etc., and to visualize activity in their sensory neurons using calcium imaging. “But we had some difficulty with the preparation,” Parrish said. So, they decided to switch gears and look at Aedes larvae, which are relatively understudied. And Parrish’s lab at UW focuses on larvae of the fruit fly, Drosophila, which provided a useful reference.

“And it was just beautiful and fascinating,” Parrish said. “We realized there was an opportunity for students in the course to make some discoveries.” They did the basic work of defining the cellular composition of the larval nervous system, reported in the present paper by three Neurobiology faculty: Parrish, Chang Yin, and Takeshi Morita. They also studied the sensory responses of different neuron populations, publication of which is forthcoming with several students contributing.

“The course gave us the opportunity to explore a new [animal] system and, with the help of all the students, get it off the ground,” Parrish said. In fact, Parrish’s home lab at UW now studies Aedes larvae, along with their Drosophila research.

“I don’t think I would have been willing to make such a large transition from what we normally do to a totally new system if I didn’t have the facilities and opportunities to explore it first in the Neurobiology course,” Parrish said.

Citation: 

Chang Yin, Takeshi Morita and Jay Z. Parrish (2024) A cell atlas of the larval Aedes aegypti ventral nerve cord. Neural Development, DOI: 10.1186/s13064-023-00178-8.