Scientists have found a major role for the glycogen synthase kinase 3 (GSK-3) gene in controlling the proliferation of neural stem cells and their differentiation into brain neurons. Their findings suggest that GSK-3 controls signals that determine how many neurons are generated in the brain during development.
The study also implies that caution should be exercised when prescribing the GSK-3-blocking bipolar disorder drug, lithium, in children whose nervous systems are still developing. The results are published in the October 4 online issue of Nature Neuroscience in a paper titled “GSK-3 is a master regulator of neural progenitor homeostasis.”
The researchers, led by William D. Snider, M.D., director of the University of North Carolina School of Medicine’s Neuroscience Center at Chapel Hill, used conditional knockout techniques to delete both alpha and beta forms of GSK-3 in developing mouse embryos. They focused on knocking out the gene at the point during mouse embryonal development during which radial progenitor cells have just been formed. Radial progenitor cells are believed to give rise to the majority of brain neurons and also to all other cellular elements of the brain.
The gene knockout resulted in the massive hyperproliferation of neural progenitors along the entire neuraxis. The radial progenitor cells were effectively locked into a constant state of proliferation. “It was really quite striking,” Dr. Snider comments. “Without GSK-3 these neural stem cells just keep dividing and dividing and dividing. The entire developing brain fills up with these neural stem cells that never turn into mature neurons. I don’t believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells.”