A new study published in Nature reveals how the genes of the jawless, eel-like parasitic fish the lamprey offer important clues about the evolution of the human brain.

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A lamprey embryo expressing the Hox gene Hoxb3 (green). In the study, Bronner and her colleagues found that Hox genes are important for hindbrain segmentation during lamprey development.
Image credit: Hugo Parker

One of the authors of the paper, Marianne Bronner, a professor of biology at the California Institute of Technology (Caltech) in Pasadena, explains that:

“Lamprey are one of the most primitive vertebrates alive on Earth today, and by closely studying their genes and developmental characteristics, researchers can learn more about the evolutionary origins of modern vertebrates – like jawed fishes, frogs, and even humans.”

Prof. Bronner is director of a unique lab in Caltech’s Beckman Institute that breeds and studies zebrafish, lampreys and Xenopus frogs, ideal subjects for the live study of molecular, cell, and developmental biology of vertebrate animals. The lab attracts scientists from all over the world.

The facility is one of only a handful of places in the world where scientists can study lampreys in captivity. Although these parasitic fish are common in the Great Lakes, they are not easy to study – they can live for 10 years before breeding, then they spawn only for a few weeks in the summer before they perish.

In the lab, the Caltech team can extend the lamprey’s breeding season to up to 2 months by adjusting the water temperature. In those extra weeks, the lampreys produce tens of thousands of additional eggs and sperm. Using in vitro fertilization, the team can generate tens of thousands of additional embryos to study.

For this latest study, Prof. Bronner and her co-authors – from Stowers Institute for Medical Research, Kansas City, MO – investigated the origins of the vertebrate hindbrain, the part of the central nervous system that we share with all chordates – organisms that have a nerve cord like our spinal cord.

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A sea lamprey in the Caltech Zebrafish/Xenopus/Lamprey Facility.
Image credit: Lance Hayashida

Vertebrates – organisms that have backbones – are a subtype of chordates whose hindbrain becomes eight segments during development, each with a unique pattern of brain circuits and function.

For example, one such segment becomes the cerebellum, which is involved in control of movement, and another becomes the medulla oblongata, which is important for breathing and other involuntary functions.

This segmentation of the hindbrain is not present in invertebrate chordates – organisms like sea squirts and lancelets, which do not have backbones.

The team were interested in a group of genes known as Hox genes, which in vertebrates contain the blueprints for the organism’s head-to-tail body plan and also control the segmentation of the hindbrain. Even though they don’t have segmented hindbrains, invertebrate chordates also have Hox genes.

The team chose to study lampreys because they occupy a unique position in the evolutionary tree between invertebrate chordates and the jawed vertebrates. Investigating Hox genes in lampreys, and whether or not they are involved in patterning of the hindbrain in the intermediate species, could give insights into how vertebrate traits might have evolved.

The team found not only that the lamprey hindbrain is segmented during development, but that Hox genes are involved, just like they are in jawed vertebrates. This surprised them, says first author Dr. Hugo Parker, of Stower’s Institute, who has spent every summer since 2008 at Caltech studying lampreys. He explains:

When we started, we thought that the situation was different, and the Hox genes were not really integrated into the process of segmentation as they are in jawed vertebrates. But in actually doing this project, we discovered the way that lamprey Hox genes are expressed and regulated is very similar to what we see in jawed vertebrates.”

This means the segmentation of the hindbrain occurs earlier in evolution than scientists had previously thought, and involves Hox genes, he says.

Dr. Parker intends to continue spending his summers at Caltech. He wants to find out what other features of the lamprey hindbrain may be conserved in today’s vertebrates. Such information is key to helping scientists understand vertebrate development.

Meanwhile, thanks to other discoveries, the lamprey is also being increasingly used as a model to understand human neurological diseases. For instance, in February 2013, scientists at the Marine Biological Laboratory in Woods Hole, MA, reported finding several lamprey genes that are also linked to human neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and spinal cord injury.