University of North Carolina scientists have identified a gene that controls the number of cells composing brain.
Called GSK-3, the gene has been found to strike a balance between two key processes - proliferation, in which the cells multiply to provide plenty of starting materials, and differentiation, in which those materials evolve into functioning neurons.
If the stem cells proliferate too much, they could grow out of control and produce a tumor. If they proliferate too little, there may not be enough cells to become the billions of neurons of the brain.
The study showed that GSK-3 controls the signals that determine how many neurons actually end up composing the brain.
The novel findings may have significant implications for people suffering from neuropsychiatric illness like schizophrenia, depression, and bipolar disorder.
"I don't believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells," Nature quoted senior study author Dr William D. Snider, professor of neurology and cell and molecular physiology, and director of the UNC Neuroscience Centre, as saying.
"People will have to think carefully about whether giving a drug like lithium to children could have negative effects on the underlying structure of the nervous system," he added.
During the study, the researchers genetically engineered mice to lack both forms of the GSK-3 gene, designated alpha and beta.
They further used a "conditional knock-out" strategy to remove GSK-3 at a specific time in the development of the mouse embryo, when a type of cell called a radial progenitor cell had just been formed.
"It was really quite striking," said Snider.
"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," he added.
GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple "signaling pathways."
They found that every one of the pathways that they studied went awry after deleting the GSK-3 gene.
The study has been published in the journal Nature Neuroscience.