November 3, 2008 

Protein that Controls Upper Motor Neuron Development Identified

Researchers funded by The ALS Association have identified a key protein that controls how stem cells in the brain become upper motor neurons. Upper motor neurons are the nerve cells in the brain that degenerate in ALS.

“This important finding will allow us to better understand how motor neurons develop in the brain,” said Lucie Bruijn, Ph.D., Senior Vice President, Research and Development of The ALS Association. “This is vital information as we try to understand the causes of ALS and as we develop new treatments targeting motor neurons.”

The researchers examined brain development in mice, and focused on a protein called Bhlhb5. While the protein had been previously identified, its role in development was unknown. They discovered that the protein was needed to turn brain stem cells into upper motor neurons. Bhlbhb5 acts within the cell’s nucleus, turning on and off other genes that build the cell into a motor neuron.

Upper motor neurons link the brain’s cortex to the spinal column. Signals sent through these neurons control muscle movements. In ALS, these neurons die off (along with the lower motor neurons of the spinal cord), leading to paralysis. Much less is known about the development of upper motor neurons compared to lower motor neurons, making the findings from this study especially significant.

The research team was led by Jeffrey Macklis, M.D., of the Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute at Harvard University in Cambridge, MA, and Lin Gan, Ph.D., of the Center for Neural Development and Disease at the University of Rochester, Rochester, NY.

The work appears in the October 23, 2008 issue of the journal Neuron.