Parasitic Fish Reveal Insights into Brain Evolution

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What can this squiggling, toothed eel-like creature possible tell us about our own brains? Well, the lamprey, although ugly, occupies a pivotal place in the evolutionary tree. Research on captive lampreys can tell us about the earliest evolution of the vertebrate brain and yield insights that may help to cure and treat neurological disease. A new study published in Nature last month suggests that the human pattern of development in an important region of our brains may have evolved much earlier than we thought, in a creature that looks much like a modern-day lamprey. So perhaps lampreys can tell us more about our brains than you might have thought!

Lampreys, sometimes called lamprey eels (although they are not eels) are an order of jawless fish, many of which are parasitic. In parasitic species the adult has a rather gruesome appearance, with a toothed, funnel-shaped mouth for sucking blood. Lampreys have been studied for decades because their simple brain architecture is though to be similar to the brains of our earliest vertebrate ancestors. Recently they’ve been attracting attention for different reasons, with studies of lamprey genetics and development being used to inform studies of neurological diseases such as Alzheimers and Parkinsons as well as revealing intriguing insights into vertebrate brain evolution. Lampreys occupy a unique position in the evolutionary tree, nestled between invertebrate chordates and jawed vertebrates. According to Professor Bronner, one of the authors of the paper, “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.”

Although Lampreys are common in the Great Lakes, they are not easy to study. They take a long time (up to 10 years) to reach reproductive maturity, and then have just a few weeks to spawn before they die, making them difficult to breed in the lab. However, Professor Bronner and colleagues at Caltech have figured out how to extend their breeding season to 2 months simply by adjusting the temperature of their water. Fish and other aquatic organisms are highly sensitive to temperature changes in the water; they use it as a calendar, triggering seasonal biological processes, including spawning. By extending the breeding season, the researchers also increased the number of eggs being produced, giving them thousands of eggs and sperm to use for in vitro fertilisation. Using this method, the team have been able to produce tens of thousands of lamprey embryos to study.

Recent research at the California Institute of Technology, one of the only places in the world where scientists can study captive lampreys, investigated the lamprey hindbrain, a region of the central nervous system shared between all organisms with a spinal cord (chordates). In vertebrates, a type of chordate, the hindbrain forms into eight segments during development, each with its own unique pattern of neural circuitry, and its own function. One segment becomes the cerebellum, involved in movement control. Another becomes the medula oblongata, responsible for involuntary movements such as breathing. Invertebrates, another type of chordate, lack this hindbrain segmentation. They still show patterning of HOX gene expression in the hindbrain, however, it’s just their HOX genes don’t cause segmentation. This led scientists to speculate that HOX-regulation of hindbrain segmentation evolved relatively recently.

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In almost all living things, a group of genes known as homeobox or HOX genes, are responsible for the head-to-tail body plan (the layout of arms, legs, eyes, antennae, segments etc). HOX genes are the blueprint for the body. In vertebrates, HOX genes are also involved in the segmentation of the hindbrain. Bronner’s team were interested in what these hind-brain-segmenting HOX genes are up to in invertebrates where there is no hindbrain segmentation.

Because of where lampreys sit on the tree of life, the team expected to find that HOX genes were not involved in the primitive hindbrain segmentation seen in lampreys. It was thought that lampreys diverged from other vertebrates so early in evolution that HOX genes hadn’t yet been coupled up with hindbrain segmentation. Using a novel method for cross-species comparison, the team at Caltech looked for shared regions of DNA between jawed and jawless vertebrates (a major divide in the vertebrate tree), comparing captive lampreys with zebrafish. Speficially, they were interested in the expression of regions that encode regulators or enhancer elements involved in segmentation. What they found was quite a surprise. Hindbrain segmentation in lampreys is regulated by HOX genes just as it is in Zebrafish, meaning that hindbrain segmentation occurred earlier in the evolution of life than previously thought, prior to the divide between jawed and jawless fish.

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