As you picture the first fish to crawl out of primordial waters onto land, it’s easy to imagine how its paired fins eventually evolved into the arms and legs of modern-day vertebrates, including humans. But a new study by researchers from the University of Chicago and the Andalusian Center for Development Biology in Spain shows how these creatures used an even more primitive genetic blueprint to develop their proto-limbs: the single dorsal, or back, fin common to all jawed fish.

The study, published this week in Nature Genetics, demonstrates that fish, mice and likely all modern-day vertebrates share genetic elements first used to develop the unpaired dorsal fin in ancient fish. They later copied these elements to produce paired appendages, like pelvic and pectoral fins, arms and legs.

“The unpaired dorsal fin is the first one you see in the fossil record,” said Neil Shubin, the Robert R. Bensley Distinguished Service Professor of Anatomy at UChicago and co-author of the new study. “Here we show that the genetic mechanisms that pattern all the fins and other paired appendages originally arose there and were redeployed to others.”

Shubin and his colleagues from Spain, led by José Luis Gómez-Skarmeta, conducted genetic analysis in mice and several kinds of fish to track the expression of Sonic hedgehog (Shh), a gene widely used in a variety of basic biological functions, but especially important in the formation of limbs.

In mice, a genetic enhancer or on/off switch called ZRS controls the expression of Shh limbs. If you knock out ZRS in a mouse, its limbs won’t develop properly. The researchers used CRISPR/Cas9 gene-editing tools to knock out ZRS in the medaka, a small, popular aquarium fish also known as a Japanese rice fish. They expected that deleting ZRS in the medaka would affect its paired fins, but instead the fish didn’t grow its unpaired dorsal fin. The paired pelvic and pectoral fins developed normally.