A group of scientists at Ohio State University has managed to observe how the brains of genetically defective zebrafish embryos develop in fine detail. Their findings could be used to help develop better treatments for disorders like autism or schizophrenia in humans.
By introducing a defective gene into zebrafish embryos they noted a distinctly different pattern of brain growth between them and normal ones. Whilst the genetic underpinnings of certain brain diseases is well established, the mechanics of how this is expressed were, until now, still a bit of a mystery.
The team found that the mutant embryos appeared to develop a distinct clustering of brain cells that may disrupt ordinary brain development and later function. This could have massive implications for treating human genetic brain disorders in the future.
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Why did they choose Zebrafish for the study?
Zebrafish, Danio rerioto give them their Latin name, are little tropical freshwater fish. They were chosen for a number of reasons by the research team.
During embryonic development, zebrafish are transparent which makes them ideal for observation. They also tend to develop at a very rapid speed and happen to share a significant amount of their genome with humans.
All of these characteristics of the species make them great testbeds for developing therapies for a whole suite of human disease, including genetic brain disorders.
What did they do and what were their findings?
Having found a viable test subject, researchers introduced a PCDH19 mutation into the embryonic zebrafish. They then observed what happened to the embryos using a high-powered microscope of their own design.
PCDH19, or Protocadherin-19, is vital for normal brain development in many species. If this gene is defective or lost it has serious implications for the developing animal.
Using this technique, they were able to observe cellular-level changes over time. And their results were very interesting indeed.
They noticed that there was a clear difference between normal zebrafish embryos and those who had the mutant gene.
Study lead James Jontes, - an associate professor of neuroscience at Ohio State and member of the university's Neurological Institute, noted on the findings: -
"This is the first study to use functional imaging at a single-cell level to explore the effects of a mutation known to cause human neurological disease in a living organism, and we saw obvious differences in the brain architecture of the animals with the mutation,"
"This type of work has the potential to help us understand in more detail the relationships between genes and diseases including autism and epilepsy. We don't understand exactly what these mutations do to brain structure and development in humans and if we can figure out what they do in fish, that will get us a long way toward some answers," he added.
How could this be used to treat humans?
In zebrafish, just like humans, the brain is composed of a large network of neurons. The healthy development of the human brain during gestation is vital for the adult's future function.
If it is affected in any way it can have serious implications for things like behavior and emotional control.
For this reason, researchers paid particular attention to the development process of the altered zebrafish embryos' neuron-level development. They found that these mutant zebrafish showed a marked increase in connectivity, or clustering when compared to the brains of ordinary zebrafish.
"We saw lots of interconnections between neurons in the mutant zebrafish. We don't know exactly what that means, but it could mean that inappropriate connections are occurring between cells that wouldn't normally interact. Maybe it becomes a problem when too many cells are incorporated into a network of neurons." Jontes noted.
Neuroscientists are fascinated by the fact that genetic mutations, like the one studied, seem to have strong genetic underpinnings, like autism. This study, and others like it, could be used to make better treatments for many genetic diseases in the future.
The study was originally published in the journal eNeuro this month.