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OHSU discovers cell in zebrafish critical to brain assembly, function

Understanding these cells (astrocytes) is key to understanding autism spectrum disorder, schizophrenia
striped silver fish swimming in blue water
By studying zebrafish larvae, scientists are learning more about the central nervous system, including the brain. Researchers were able to identify the presence of astrocytes from a stem cell, and watch the entire development, which has never been visualized before in a vertebrate animal. (Getty Images)

New research from Oregon Health & Science University for the first time documents the presence of astrocytes in zebrafish, a milestone that will open new avenues of research into a star-shaped type of glial cell in the brain that is critical for nearly every aspect of brain assembly and function.

The research was published this week in the journal Nature Neuroscience.

With their transparent bodies, zebrafish larvae provide a unique opportunity to gaze into the inner workings of the central nervous system, including the brain, even in living animals. The identification of astrocytes and the generation of tools to work with them in zebrafish will enable researchers around the world to open new lines of research to advance scientific understanding of how astrocytes function.

Astrocytes, it turns out, are the most abundant and mysterious cell type in the human brain, and OHSU is becoming a hub for research into their roles in development, brain function and disease.

Kelly Monk, Ph.D. sitting at a microscope
Kelly Monk, Ph.D., in her lab at the Vollum Institute. (OHSU/Kristyna Wentz-Graff)

“There is no neurodegenerative disease that I know of where astrocytes are not profoundly affected in some way,” said senior author Kelly Monk, Ph.D., professor and co-director of the Vollum Institute at OHSU. “This gives us a powerful tool to get a handle on what these cells do and how they do it.”

Monk and co-author Marc Freeman, Ph.D., credit lead author Jiakun Chen, Ph.D., a post-doctoral researcher in the Monk and Freeman labs, with developing a panoply of tools, including a cell-specific approach using the gene editing tool CRISPR to label and manipulate astrocyte precursors and incisively study their development and functions.

“He was able to capture the birth of an astrocyte from a stem cell and its entire development, which has never been visualized before in a vertebrate animal,” Monk said.

green glowing blobs on a black background, with the astrocyte noted in pink
This series of photos shows the development of a single astrocyte in the zebrafish spinal cord, starting from a progenitor cell in a fish two-days old, ending with a fish at nine days old. (OHSU)

Freeman said the discovery will dramatically enhance the study of how glia regulate brain development and physiology.

“This opens the door to experiments that you can’t do in any other organism,” Freeman said. “Zebrafish is the only animal in which you can now live-image all types of vertebrate glial cells – astrocytes, microglia, oligodendrocytes and OPCs – along with any neuron in intact neural circuits, from the earliest stages of development. Zebrafish is also the only vertebrate in which you can image the entire brain in live, behaving animals to figure out how it works. Understanding the role of these cells (astrocytes) in brain development will be key to understanding devastating neurodevelopmental disorders like autism spectrum disorder and schizophrenia.

“It’s a major step forward and should power a lot of exciting work in the coming years.”

Support for the research was supported by the National Institutes of Health, award R01NS099254, R37NS053538 and R21NS115437.

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