Scientists reconstruct history of vertebrate brain

Chinese scientists have constructed the first three-dimensional, single-cell atlas of the entire lamprey brain, providing new evidence on how the vertebrate brain evolved over hundreds of millions of years. 

The study, led by Su Bing from the Kunming Institute of Zoology of the Chinese Academy of Sciences, together with researchers from BGI Research and Liaoning Normal University, was published in June as a cover study in the journal Science.

The atlas provides a high-resolution molecular map showing where individual cells are located across the lamprey brain and which genes are active in them.

Lampreys are among the few surviving jawless vertebrates. Their basic body plan has largely remained unchanged in the fossil record for about 360 million years, making them an important reference for reconstructing the ancestral vertebrate brain.

When researchers compared the lamprey brain atlas with that of a mouse, they found striking similarities in gene-expression patterns and functions across multiple brain regions, despite hundreds of millions of years of evolutionary separation.

The finding suggests that the common ancestor of vertebrates may already have possessed a well-organized and molecularly complex brain, Su said.

At the same time, different evolutionary lineages developed their own distinct features. Lampreys, for example, have unique midbrain neurons and unusually large Muller cells — glial cells found in the retina — while mammals evolved a highly elaborate, layered cerebral cortex.

The researchers then compared genomic and molecular data from a range of vertebrates, including zebrafish, turtles, lizards, zebra finches, pigeons, mice and macaques, to examine how neurons became more specialized over time.

One important clue came from a type of neuron found in lampreys known as the anamniote-enriched neuron, or AEN.

Unlike most specialized neurons, AENs express molecular markers associated with both excitatory and inhibitory signaling, allowing them to perform what researchers describe as "moonlighting" functions.

Such versatile neurons are common in lampreys and zebrafish but become rare in amniotes, where neurons with more specialized functions predominate.

The researchers found that the emergence of these "specialist" neurons coincided with an ancient second round of whole-genome duplication in the common ancestor of jawed vertebrates.

"Whole-genome duplication essentially doubled the genetic repertoire," Su said. A larger genetic "toolkit", he added, may have provided the raw material needed for neurons to diversify into more specialized types with distinct functions.

The atlas also offered new clues to another long-standing question: when did the cerebellum emerge?

Researchers identified cells in a "cerebellum-like region" of the lamprey brain that are molecularly similar to interneurons in the zebrafish cerebellum. The finding indicates that a primitive form of the cerebellum may already have existed in early vertebrates, providing new molecular evidence in the debate over its evolutionary origins.

Beyond reconstructing the history of the vertebrate brain, Su said the research could eventually offer insights for artificial intelligence.

Modern AI systems seek to emulate aspects of human brain function, yet scientists still have a limited understanding of how the brain itself works, he said.

"If we understand how the human brain evolved step by step, it can help us better understand how it works," Su said. "That, in turn, could provide important references for the design of AI software and hardware."

Exploring those connections will be one focus of the team's future research, he added.