Little Big Fish

A relative of the minnow makes a sizable splash in an MU laboratory.

Model organisms are essential to scientific investigations of all sorts, especially those exploring human development and disease. The relatively complex physiology of rats and mice, for example, allow these rodents to play a crucial role in testing drug therapies for humans. Simpler organisms, such as the microscopic worm C. elegans, are great for teasing out basic questions related to gene expression and regulation.

And then there is the zebrafish, a home-aquarium staple that, in the wild, populates the freshwater rivers and streams of Northern India and the Himalayas. Since the early 1970s, this relative of the minnow has come to play a supersized role in biomedical science. It’s a star turn due, in part, to a curious characteristic: Zebrafish produce embryos that are fully transparent.

Having see-through offspring is advantageous because it allows researchers to observe first hand much of the fishes’ morphological development, from initial cellular movements to organ formation. When coupled with a little genetic tinkering, most notably the “labeling” of particular groups of cells with the fluorescing jellyfish protein GFP, no other vertebrate model organism has proven more useful.

Just ask MU’s Anand Chandrasekhar, a professor of biological sciences. Chandrasekhar is using the fish to advance our understanding of human disorders such as spina bifida, a birth defect in which the neural tube comprising the spinal cord fails to close properly during pregnancy. In its severe forms, spina bifida can be debilitating. According to the National Institutes of Health, it affects one in every 2,000 children born in the United States.

“We are studying how neurons move to their final destinations,” Chandrasekhar says of his recent work. “It’s especially critical in the nervous system because these neurons are generating circuits similar to what you might see in computers. If those circuits don’t form properly, and if different types of neurons don’t end up in the right locations, the behavior and survival of the animal will be compromised.”

Chandrasekhar and his research team have focused on motor neurons located in the zebrafishes’ hindbrain, a location that corresponds to the human brainstem. In the fish, these neurons control gill and jaw movement. The genes responsible for the development and organization of these neurons, Chandrasekhar says, are functionally similar to genes in higher vertebrates, including mammals.

“One of the hallmarks of spina bifida is an open neural tube in the spinal cord,” he explains. “The cells closing the neural tube actually know left from right, and front from back, just like the neurons migrating to their appointed places in the zebrafish hindbrain. Additionally, mutations in many genes that result in defective neuronal migration can lead to defects in neural tube closure. We anticipate that understanding the genes and mechanisms controlling neuronal migration in zebrafish will shed light on the mechanisms of human neural tube closure, and why this process goes awry in spina bifida.”

Chandrasekhar’s most recent work appeared in the February 2014 issue of the journal Mechanisms of Development. A related study was published in the October 2013 issue of Developmental Biology.


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