The “Sonic hedgehog” gene plays the same role in human limb development and gill development in cartilaginous fishes like sharks and skates, says a new study published on April 19 in the journal Development. Named after the video game character, the gene dictates the identity of each human finger and maintains limb skeleton growth in the same way it helps branchial rays or gill arches development in skate embryo.

This suggests that human limbs share a genetic programme with fish gills. The study supports the influential German anatomist Karl Gegenbaur’s controversial theory in 1878. However, the theory has been overlooked due to lack of evidence, until now.

“Gegenbaur looked at the way that these branchial rays connect to the gill arches and noticed that it looks very similar to the way that the fin and limb skeleton articulates with the shoulder,” says Andrew Gillis from the University of Cambridge’s Department of Zoology and the Marine Biological Laboratory. “The branchial rays extend like a series of fingers down the side of a shark gill arch.”

Sonic hedgehog

A skeletal preparation of an embryonic bamboo shark. This image is a ventral view (so looking at the underside of the embryo) with the head to the top, and you can nicely see the gill arch appendages projecting off each side of the head, just in front of the fins. Credit: Andrew Gillis

“In a hand, for instance, Sonic hedgehog tells the limb which side will be the thumb and which side will be the pinky finger. In the later stages of development, Sonic hedgehog maintains outgrowth so that the limb grows to its full size,” adds Gillis.

When the researchers interrupted the gene during early embryo development, the branchial rays grew on the wrong side of the gill arch. Interrupting it at a later stage of development reduces the number of branchial rays. Both effects can be observed in human limb development.

“Either way this is a fascinating discovery, because it provides evidence for a fundamental evolutionary link between branchial rays and limbs,” says Gillis.

It turns out that other scientists ignored Gegenbaur’s theory because they only studied mice, zebrafish and other animals that do not have branchial rays. Moreover, unlike other scientists, the new team’s approach is to study and compare anatomical features of all animal species instead of limiting themselves into specific animals, which could also limit the understanding of genetic control of anatomy evolution.

The researchers are currently exploring deeper into Gegenbaur’s theory by comparing other genes involved in human limb development with the other genes involved in the gill development of fish.