City of Hope neuroscientists have found a key mechanism that controls how neural stem cells mature into brain cells. The findings, published recently in the Journal of Neuroscience, shed more light on some of the most basic steps behind brain development and could lead to future treatments for brain diseases.
|Qiang Lu (Photo by Paula Myers)|
Stem cells are the source of all types of cells in the body. Neural stem cells can either develop into various types of brain and nerve cells, a process called differentiation, or they can maintain themselves as stem cells and wait until the body needs them to mature.
Neural stem cells are critical to the development of all parts of the brain, including the cerebral cortex — the brain region in mammals (including humans) that controls advanced functions such as muscle movement, the five senses, language and even conscious thought.
Neural stem cells differentiate to form the cerebral cortex as an embryo develops. Until recently, the control mechanisms that help neural stem cells maintain themselves or differentiate into cerebral cortex brain cells remained unclear, but a team led by Qiang Lu, Ph.D., assistant professor in the Department of Neurosciences, has uncovered an important new clue to the process.
The researchers found that a protein called ZHX2, short for zinc-finger and homeodomain protein 2, links with another protein called ephrin-B1 to control key genes in the neural stem cells.
In previous research, the team found that ephrin-B1 was critical to keeping stem cells in their early, undeveloped stages; however, the researchers lacked the other half of the equation — the trigger that could cause the stem cells to differentiate when needed. They suspected another molecule could be involved, and their hunch was supported by research that showed ephrin-B1 might link with another protein.
Lu and his team set out to find proteins that might interact with ephrin-B1, and their search led them to ZHX2.
The researchers found ZHX2 could bond to ephrin-B1, providing a counterbalance to ephrin-B1’s tendency to keep stem cells from maturing.
“We found higher levels of ZHX2 in maturing neural stem cells,” said Lu. They also found that interfering with the levels of ZHX2 caused the neural stem cells to behave abnormally.
“ZHX2 is clearly very important to brain development,” said Lu. “What we want to do now is identify which genes ZHX2 affects to better understand this complex process and possibly how to influence it.”
Other researchers on the study, published June 10, include postdoctoral fellows Runxiang Qiu, Ph.D., and Kiyohito Mura, Ph.D., Jun Wang, graduate student in the Irell & Manella Graduate School of Biological Sciences, Heying Zhang, M.D., research associate, and former graduate student and lead author Chen Wu, Ph.D.