Researchers have revealed how a genetic circuit may have helped the evolution of insect wings.
In most developing tissues, signals called morphogens act like lighthouses, guiding nearby cells towards their fate and telling them what to become. Each cell relies on such signals for organised structures like organs and limbs to form. But as Jean-Paul Vincent explains, “for life to evolve large structures, those signals need to reach particularly far.”
JP leads a team of developmental biologists at the Crick, studying how cells interact to form organs during development. They investigate this process in fruit flies, because there are established ways to track and manipulate gene function, making it possible to trace morphogen signals with remarkable precision.
In new research published in Current Biology, the team identified a signalling feedback loop which they think may have been vital to the evolution of insect wings and therefore flight.
For the study lead and postdoctoral scientist Anqi Huang, there was one morphogen of interest. “Dpp is a signal that exists at different concentrations across a fruit fly wing and we know it’s key to wing development.
“Since wings are isolated pieces of tissue within developing larvae, they do not benefit from signals coming from elsewhere in the animal. I was interested in how the Dpp signal can reach cells throughout the whole wing, including those that are far from the source.”
Anqi found that as the Dpp signal decreases across the tissue, another molecule called Brinker forms a reverse gradient. This gradient forms solely in response to the Dpp gradient. The brinker gene is repressed by Dpp and is therefore increasingly expressed as the Dpp signal becomes weaker.
“We began to investigate how the smooth Brinker gradient can form despite the weak and noisy nature of the Dpp gradient far from its source,” adds Anqi, who teamed up with physicists Luca Cocconi, Ben Nicholls-Mindlin and Guillaume Salbreux, to discover that Brinker is at the core of a feedback circuit.
“Once established, the reverse gradient of Brinker takes over as the main determinant of cell positional information, far from the source of Dpp,” she describes.
The team were curious about when, during evolution, Brinker became important to boost the reach of Dpp. “This took us down an evolutionary rabbit hole,” describes Anqi.
Insects were the first animals to evolve wings, but some have remained wing-less, for example, the firebrat, pictured here next to a fruit fly.
“We first looked at publicly available genome sequences to find out which animals have the brinker gene. And we could see a clear line – brinker was only found in insects and is not present in closely related crustaceans.”
Insects were the first animals to evolve wings, but some have remained wing-less, for example, the firebrat, a member of the Zygentoma order. Anqi was keen to find out if firebrats have the brinker gene, and whether the Brinker protein also makes a reverse gradient in this species.
For this part of the investigation, she needed the firebrat genomic sequence, which is about as large as the human genome. Through discussions with scientists in the Crick’s Genomics facility, she found that researchers working on the Tree of Life project at the Sanger Institute were about to complete the firebrat genome sequence.
Armed with the information necessary to show that brinker exists in this wing-less species, she then performed additional experiments to show that, in firebrats, Brinker does not form a gradient and is as yet unconnected to the Dpp signal transduction.
This suggests that the Brinker-mediated feedback circuit may have been an evolutionary innovation of winged insects.
“Insects were the first animals to evolve flight, around 400 million years ago, approximately the time when trees first appeared on our planet,” adds JP.
“Therefore, the incorporation of Brinker into the Dpp signalling network coincided with insects’ ability to explore new habitats above ground and thus to become one of the most successful classes in the tree of life.”
