Role of the ATM protein in neurogenesis

Ataxia telangiectasia (AT) is a recessive childhood disease caused by mutations in the ATM (AT-mutated) gene. The hallmark of the disease is progressive neurodegeneration that eventually affects all areas of the brain. It is known that the ATM protein initiates a cascade of signalling events that leads to cell-cycle arrest and DNA repair in response to ionising radiation. Its role in the nervous system is not clear.

In the 1 March Genes & Development, researchers led by Carrolee Barlow of the Salk Institute for Biological Studies, La Jolla, California, report that neural progenitor cells lacking ATM show a blunted response to environmental stimuli that would normally result in proliferation, survival and differentiation along a neuronal lineage (Genes Dev 2001, 15:554-566).

They found that neuronal stem cells in the hippocampus of ATM-/- mice had an abnormally high basal rate of proliferation. In wild-type mice, environmental stimulation, such as the use of ...