NIH grant supports study of central nervous system’s precise connections

March 4, 2019 | News, Research, UToday, Natural Sciences and Mathematics
By Tyrel Linkhorn

A University of Toledo researcher who studies embryonic development has received a $448,500 research grant to further understanding of how the central nervous system’s extraordinarily precise connections are made in the first few weeks of life.

With that information, it might be possible to address brain disorders such as epilepsy, schizophrenia and dyslexia during development, or to rewire the central nervous system in people who have had strokes or spinal cord injuries.


The three-year grant from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development will enable Dr. Guofa Liu, associate professor in the UT Department of Biological Sciences, to study the role of microRNA in mapping the central nervous system.

The brain and spinal cord each have two sides, which link together to control everything from movement to the sense of touch.

Those connections between the two sides are made early. Commissural neurons in a developing embryo send out a tiny fiber known as an axon that finds its way to a corresponding target cell to link the two sides of the central nervous system.

Scientists know there’s a process that works almost like a relay race as the axons cross the midline of the central nervous system. As the axon approaches and crosses the embryonic midline, there’s a sort of molecular switch that hands off guidance from one side of the central nervous system to the other.

“Axon pathfinding is very important for early development of the nervous system, but we don’t know much about the switch that pushes or pulls the nerve fiber to make the right connections,” Liu said. “If we find that mechanism, we may be able to find a way to rescue defects in axon guidance that lead to neurodevelopmental disorders.”

MicroRNA are tiny molecules that work as biological programming to regulate gene expression. Liu’s previous research has suggested they play a key role in the handoff as axons cross from one side of the central nervous system to the other.

Work funded by the new grant will dig deeper into how that molecular switch actually works.

Beyond understanding how the central nervous system develops, the new knowledge could be applied toward nervous system regeneration in individuals impacted by paralysis.

“If we find the mechanics that can promote axon growth and reach the proper target, that could give us potential treatment for stroke or brain trauma patients,” he said. “Currently, there are some clinical methods to create axon growth, but because scar tissue can create a barrier, the axon cannot reach the right place. Even if they can grow past the scar, they don’t know where to go. Understanding this mechanism and the role microRNA plays might allow us to help route the axon pathways.”

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