As the only mammals that can fly, bats have always been something of an evolutionary puzzle: They use sound waves to navigate their world. They hang upside down. And they have large webbed wings in place of spindly front legs.
“It looks like bats sort of jump out of nowhere,” said Nadav Ahituv, a researcher at UC San Francisco. “There’s no close ancestor where you can see the evolutionary process.”
But the extreme differences in bats’ limbs, Ahituv said, make them the perfect subjects for studying a larger biological question: What makes some limbs long and lanky but others short and stubby?
The findings from Ahituv’s two recently published studies on bats’ wings might help us better understand how our own arms and legs develop — and perhaps someday even allow doctors to correct medical conditions where that process has gone awry.
“We’ve spent decades trying to understand the general principle of how limbs develop,” said Kim Cooper, a biologist at UC San Diego who wasn’t involved in the work. But, she added, we still don’t really understand what distinguishes, say, an arm from a leg. Why is one shorter than the other?
This is partially because most studies on limb development have been done on animals like mice, said Ahituv, an associate professor at the UCSF School of Pharmacy.
Because each of a mouse’s four legs is quite similar, studying them doesn’t tell us much about what makes different limbs take on unique shapes.
That’s where bats are useful. Their hind legs develop much like those of a mouse or human embryo. And so do their front legs — at first. As the embryonic bat grows, though, that begins to change: The digits of its front legs become much longer.
“During development, your hands start off like a paddle,” said Nicola Illing, a collaborator at the University of Cape Town, South Africa. That tissue usually gradually goes away, leaving fingers behind — but not always.
In bats, “one of the first differences we see is that tissue regressing in the hindlimb but not the forelimb,” Illing said. The left-behind webbing helps make the forelimbs look like wings.
The sharp differences between bats’ wings and legs mean that scientists can compare the two to easily see what’s changing in each one during development.
Ahituv, Illing and their colleagues are studying the genes that control these processes, and when they’re switched on and off.
The entire process of development in any animal requires many such switches, like a coordinated Christmas-light show. The genes that make eyes, ears, legs and arms must be turned on at the right time and in the right place in the body.
When things go wrong, it shows: Limbs might be attached in the wrong places; fingers might not form.
The researchers wanted to figure out what genes and switches specifically controlled bats’ wings. So Illing collected Natal long-fingered bats at different stages in development from a South African cave. Then the team measured which genes were expressed differently in the forelimbs versus the hindlimbs, both before and after the forelimbs started looking more like wings.
Instead of just one master switch controlling the wing development, they found an entire circuit box, they reported recently in the journal Nature Genetics.
“It’s not just one pathway and one gene,” Ahituv said. “It’s a combination of pathways involved in skeletal growth, neuronal development, cell death” and other processes.
In a second study, published the same day in the journal PLOS Genetics, the scientists examined particular regions of DNA that were common across mammals — and then looked to see where bats’ DNA was dramatically different. Those stretches of DNA might contain genes for bat-specific traits like wings.
Ahituv says many of the genes controlling wing development in bats are the same that control limb development in humans. They’re just turned on and off at different times.
That means studying bat limbs could also help us better understand human ones.
Contact Laurel Hamers at lhamers@mercurynews.com and follow her on Twitter at @Arboreal_Laurel.
