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UNC study pinpoints gene controlling number of brain cells
Date:10/4/2009

he most studied kinases or signaling molecules in all of biology.

The researchers 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.

As the brain develops, neural stem cells evolve through three different stages -- neural epithelial cells, radial progenitor cells and intermediate neural precursors. The radial progenitor cells are especially important because they are thought to provide the majority of the neurons of the developing brain but also differentiate themselves to give rise to all the cellular elements of the brain. The researchers discovered that deleting GSK-3 during this second phase of development caused the radial progenitor cells to be locked in a constant state of proliferation.

"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."

GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple "signaling pathways." Thus, the researchers looked to see what effect deleting the molecule had on some of these pathways. They found that every one of the pathways that they studied went awry.

Snider and his colleagues now want to see if adding GSK-3 back to their genetically engineered mice can convert the proliferating stem cells into neurons, possibly resulting in three to four times as many neurons in the mutants as normal.

"I find that quite interesting because I can't think of any other manipulation that potentially would enable you to simply dial up and down the number of neurons that are generated in the brain," said Snider.


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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert

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