The researchers found that mice whose brains were severely damaged by loss of the genes "Numb" and "Numblike" in one region just after birth showed substantial mending within weeks. They attributed that repair to neural stem cell "escapees" that had somehow retained or restored the genes' activity and, with it, their regenerative potential.
"At two weeks, the knockout animals' brains had developed a big hole," said Yuh-Nung Jan, a Howard Hughes Medical Institute investigator at the University of California, San Francisco. "We thought that the mice would not live long, but by four weeks, the hole was largely repaired and the animals survived.
"It was a big surprise. It was not known that the brain has this kind of ability to repair itself."
Jan and his colleagues first discovered Numb in the fruit fly Drosophila more than 10 years ago. The gene was found by them and others to play a role in determining the fate of neuroblasts, cells that develop into neurons or other support cells in the insects' brains. Later, researchers found two functionally related mammalian proteins, dubbed Numb and Numblike, to be critical in the development of neurons in embryonic mice.
To investigate the genes' role after birth, Jan's team developed mice in which Numb and Numblike could be turned off only in a portion of the brain termed the subventricular zone (SVZ) when they administered a particular drug. The SVZ is known to be a site, or niche, that contains neural stem cells after birth.
In newborn mice, loss of the genes left the SVZ "greatly disturbed," Jan said.
Their results indicated that Numb and N