Grove Lab explores the secret origin of the vertebrate brain

The acorn worm is an eye-less, ear-less invertebrate that lives in the intertidal zone, scavenging food particles from the sand and water. One wouldn’t expect to find the developmental clues for the creation of the vertebrate brain in such a humble creature. But a new study led by a University of Chicago graduate student and published today in Nature finds that the signals that shape the brains of all vertebrates, including humans, can indeed be traced back to the ancestor we share with the acorn worm.

Perhaps due to a touch of vertebrate bias, human scientists have long looked for what biological factors separate the vertebrate brain from the simpler nervous system found elsewhere in the animal kingdom. When physically compared to the nervous system of invertebrate chordates, the brain of vertebrates stands out for its complex structure and specialized regions. But when researchers compare the genetics underlying nervous system development in these two groups, there are fewer differences than expected.

Notable exceptions are the “signaling centers,” areas of the vertebrate embryo that secrete factors to organize the elaborate construction of the brain and spinal cord. The lack of these centers or their associated genes in commonly used model invertebrate organisms suggested that they were the unique property of vertebrates.

“Based on the available data, the idea that these signaling centers could have been responsible for the morphological innovations in vertebrate brains was very compelling,” said Ariel Pani, graduate student in the University of Chicago Committee on Evolutionary Biology. “Scientists went looking for them in amphioxus and ascidians, but they were for most part either absent or divergent, which supported the hypothesis about their origin in vertebrates.”

"We study these signaling centers so much in the vertebrate central nervous system", said Elizabeth Grove, "that we were really excited to see evidence that the same signaling molecule centers existed millions of years ago, organizing the body plan before there even was a CNS".

But while modern-day amphioxus and ascidians are used as models for the ancient species that closely preceded the first vertebrates, it’s possible that they could have lost those signaling centers in the over 500 million years since they shared a common ancestor with their brainier vertebrate relatives. Pani, now completing his research at Stanford University in the laboratory of Christopher Lowe, decided to look at a slightly more distant relative of vertebrates, represented by Saccoglossus kowalevskii, a modern acorn worm.

Collected by the researchers at the Marine Biological Laboratory in Woods Hole, Massachusetts, acorn worms don’t resemble likely suspects for investigating the origin of the vertebrate brain. In fact, acorn worm embryos don’t have what could classically be called a brain at all, instead displaying a diffuse, circumferential organization…with some unique features.

“Their nervous system is still very controversial,” Pani said. “It has historically been described as diffuse, with neurons throughout the skin. But what people found most recently is that isn’t quite the case, as there is a dorsal nerve cord in adult animals with potential homology to the chordate nerve cord.”

Yet when Pani and collaborators in the laboratory of Elizabeth Grove, professor of neurobiology at the University of Chicago Biological Sciences, looked at gene expression in the acorn worm embryo, they found a surprise. Three signaling centers thought to be exclusive to vertebrates — ANR, ZLI, and IsO — were present and active in the developing acorn worm…just not performing their usual jobs. By blocking functions of several genes associated with the signaling centers one by one, the researchers discovered that they controlled the development of different regions in the acorn worm body instead of the formation of the nervous system specifically. Other than the ultimate anatomy, the signaling centers direct development in much the same way as they do in modern vertebrates — strong evidence for their evolutionary relatedness.

“That’s really the most conclusive support for homology between these signaling centers,” Pani said. “The gene expression is very similar, and it is also regulating regionalization of the body in a similar way.”

(see full article and Press Release)