The most dangerous animal in the world just became easier to study—and perhaps one day, easier to defeat. Researchers from Rockefeller University’s Laboratory of Neurogenetics and Behavior, in collaboration with mosquito experts worldwide, have unveiled the first-ever cellular atlas of the Aedes aegypti mosquito. This species transmits more diseases than any other mosquito. The Mosquito Cell Atlas offers cellular-level resolution of gene expression across every mosquito tissue, from antennae to legs. Published in the journal Cell, the dataset is freely available to researchers and the public.
“This is a comprehensive snapshot of what every cell in the mosquito is doing as far as expressing genes,” said Leslie Vosshall, lab head and a veteran researcher of the yellow fever mosquito for nearly two decades. “It’s a real achievement because we profiled so many different types of tissues in both males and females.”
A New Era in Mosquito Research
The atlas has already provided new insights into the genetic secrets of Aedes aegypti, revealing novel cell types, subtle differences—and unexpected similarities—between male and female mosquitoes. It also highlights dramatic changes in genetic expression in the female mosquito brain after a blood feeding.
Senior author Nadav Shai, a senior scientist in Vosshall’s lab and at the Howard Hughes Medical Institute, anticipates the atlas will be a catalyst for new discoveries. “We believe this enormous data set will really move mosquito biology forward,” he stated. “It’s a great tool for vector biologists to explore their interests and pursue new research directions.”
Organ by Organ: A Collaborative Effort
In recent years, scientists have employed single-cell sequencing to identify cell types and illuminate gene expression patterns in model organisms like Drosophila melanogaster (fruit fly) and Mus musculus (mouse). Mosquito researchers have followed suit, albeit in a piecemeal fashion—organ by organ, tissue by tissue. This project, however, represents a comprehensive approach.
Most previous studies focused on female mosquitoes, often neglecting males. “Both females and males feed on nectar, but females need blood to develop eggs,” explained first author Olivia Goldman. Vosshall added, “We wanted to be inclusive and fill the gap in male mosquito biology.”
The team employed single-nucleus RNA sequencing (snRNA-seq) to capture the biology of all insect cell types, creating a dataset of over 367,000 nuclei from 19 mosquito tissues. These were selected across five biological themes: major body segments, sensation and host seeking, viral infection, reproduction, and the central nervous system.
Discovering New Sensory Capabilities
Among the most striking findings was the prevalence of polymodal sensory neurons—cells capable of detecting a wide array of environmental cues, including temperature and taste. Previous research identified these neurons in the antennae and maxillary palps, but the new atlas reveals their presence throughout the mosquito’s body, including in the legs.
“Just like the antennae and maxillary palps, the legs and mouthparts have powerful tools for sensing the world,” Shai noted. “These chemoreceptors allow mosquitoes to detect sweetness and fresh water, essential for survival.”
Brain Changes and Behavioral Shifts
After feeding, a female mosquito loses interest in humans and focuses on egg development. “How does this drive to bite people get turned off?” Vosshall pondered. The team examined gene expression in female mosquito brains at intervals after blood feeding, discovering dramatic changes that peaked early and gradually diminished.
“The glia are completely rewired during this time when the females lose interest in people,” Vosshall revealed. This unexpected finding highlights the importance of glia in behavior.
Implications and Future Directions
Despite documented differences between male and female mosquitoes, their cellular makeup is largely identical, aside from small clusters of sex-specific cells. “We expected a tale of two genomes, but that’s not what we found,” Vosshall admitted.
The Vosshall lab will continue to mine the mosquito single-cell atlas to investigate behaviors such as host seeking and environmental sensing. “Different people in the lab are going to take it to different places,” Shai said, expressing hope that researchers worldwide will find inspiration in the dataset.
“This is a global resource that has been open to everyone since the project’s inception in 2021,” Vosshall added. “We’re excited to see the discoveries that will come from it.”
