How the gut got its villi

Comparing species, researchers at Harvard SEAS and Harvard Medical School investigate a process they dub "villification"

"You are not just a ball of cells," says Clifford Tabin, George Jacob and Jacqueline Hazel Leder Professor of Genetics at Harvard Medical School (HMS).

The way cells organize within the human body allows us all to function the way we do, but a couple of Harvard professors are concerned as much with that developmental process as with the end result. Tabin shares a common perspective with L. Mahadevan, the Lola England de Valpine Professor of Applied Mathematics at the Harvard School of Engineering and Applied Sciences (SEAS), professor of organismic and evolutionary biology, and professor of physics.

"When I teach medical students, they're more interested in the rare people who are born with birth defects," says Tabin. "They want to understand embryology so they understand how things go awry, but I’m more interested in the fact that for everyone sitting in my classroom - all 200 of those medical students and dental students - it went right! And every one of them has a heart on the left side and every one of them has two kidneys, and how the heck do you do that?"

By taking steps back through embryos' development, researchers in Mahadevan's and Tabin's laboratories investigated how the guts of several different animals end up as they do. Their findings, published in a recent issue of Science, reveal that the principles guiding the growth of intestinal structures called villi are surprisingly similar across chickens, frogs, mice, and snakes.

These fingerlike villi lie on the inside wall of the gut and are crucial in the uptake of nutrients from food by effectively increasing the absorptive surface area 30-fold.

Researchers in Tabin's lab had noticed a zigzag pattern on the inside of the guts of chick embryos, while collaborating on a project that investigated the coiling of the gut.

"They showed me the picture and I said, ‘I know how to explain that,'" recalls Mahadevan, who had studied the cause of such zigzag patterns in shrinking gels in 2005.

Mahadevan's group uses theoretical and experimental approaches to study a variety of problems in science and engineering, with a recent interest in the physical basis of morphogenesis in plants and animals, while Tabin's team has a longstanding interest and expertise in the development of living organisms. Together, the groups designed and carried out experiments and simulations to elucidate exactly what makes the villi turn out the way they do, a process they dubbed "villification."

Previous studies into villi development only looked at the later stages of their growth, which is driven by stem cells in the structures' bases, but by pooling their expertise, the two labs postulated and confirmed that early villus growth is driven not by stem cell generation but by mechanical forces from the different muscle layers of the gut.