The sea lamprey, a 500-million-year-old animal with a sharp-toothed suction cup for a mouth, is the stuff of nightmares. A new study from the Storrs Institute for Medical Research has discovered that the part of the brain that controls vital functions such as blood pressure and heart rate in both sea lamprey and humans has remarkably similar molecular and genetic makeup. Created using the toolkit.

On February 20, 2024, research from the lab of investigator Rob Krumloff, Ph.D., was published. Nature Communications Provides a glimpse into how the brains of ancient animals evolved. The team unexpectedly revealed that a key molecular signal is required during brain development in a very broad range of vertebrates.

“This study on the hindbrain is essentially a window into the distant past and serves as a model for understanding the evolution of complexity,” said co-author Hugo Parker, Ph.D.

Like other vertebrates, sea lampreys have a backbone and a skeleton, but they are notably missing one feature of their head — a jaw. Because most vertebrates, including humans, have jaws, this striking difference in sea lampreys makes them a valuable model for understanding the evolution of vertebrate traits.

“500 million years ago there was actually a split between jawless and jawed vertebrates,” said Alice Bedois, PhD, a former predoctoral researcher in the Krumlov lab and lead author of the study. “We wanted to understand how the vertebrate brain evolved and whether there was something unique about jawed vertebrates that their jawed relatives didn’t have.”

Krumlauf Lab at the California Institute of Technology and Marianne Bronner, Ph.D. Previous work from the Kay lab indicated that the structure and subdividing genes of the sea lamprey hindbrain are similar in jawed vertebrates, including humans.

However, these genes are part of an interconnected network or circuit that needs to be initiated and instructed to build the brain properly. New research identifies a common molecular signal, while known for head-to-tail patterning in a wide range of animals, as part of the gene circuitry that guides hindbrain patterning in sea lampreys. .

“We found that not only the same genes but the same signal are involved in sea lamprey hindbrain development, suggesting that this process is ancestral to all vertebrates,” Bedois said.

This indicator is called retinoic acid, commonly known as vitamin A. While researchers knew that retinoic acid signals gene circuitry to form the hindbrain in complex species, it wasn’t thought to be involved in more primitive animals like the sea lamprey. Surprisingly, they found that the sea lamprey core hindbrain circuit also starts with retinoic acid, providing evidence that these sea monsters and humans are more closely related than expected.

“People thought that because sea lampreys lacked a jaw, they didn’t have a forebrain like other vertebrates,” Krumloff said. “We’ve shown that this core part of the brain is structured in exactly the same way as mice and even humans.”

There are well-known signaling molecules that inform the fate of cells during development. Now, researchers have found that retinoic acid is another key player in signaling important developmental steps such as brain cell formation. Also, if hindbrain formation is a conserved feature for all vertebrates, other mechanisms must be responsible for explaining their incredible diversity.

“We are all descended from a common ancestor,” Bedouis said. “Sea lampreys provide an additional clue. We now need to look further back in evolution to discover when the gene circuitry that controls the formation of the hindbrain first evolved.”

This work was funded by institutional support from the National Institute of Neurological Disorders and Stroke (Award: R35NS111564) of the National Institutes of Health (NIH) and the Storrs Institute for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.