A University of California - San Francisco (UCSF) study has found that a specific signaling link between neurons and muscles in the fruit fly is essential for keeping the insect's nervous system stable.
The findings are relevant for ongoing research in identifying causes and developing treatments for neuromuscular neurodegenerative diseases in humans, such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, says study co-author Graeme Davis, PhD, associate professor and vice chair of the Department of Biochemistry and Biophysics at the University of California, San Francisco.
"If we want to make new drugs to treat neurodegenerative disease, then we have to identify new drug targets, and our study findings present that potential," he says. "This study is a significant step forward because we have shown that a signaling system composed of several genes is important for keeping the nervous system stable."
The findings are reported in the September issue of the journal Neuron.
The nervous system is a complex pattern of connections that exists for the entire life of the organism, and understanding how the myriad patterns and pathways of these connections are maintained for long periods of time presents an ongoing challenge to scientists, says Davis.
Davis and co-author Benjamin Eaton, PhD, a post-doctoral fellow in Davis' lab, were led to the new discovery through ongoing experiments with a signaling system in fruit flies that is tied to a protein called bone morphogenetic protein, or BMP. They found that the BMP signaling system is required for the long-term stability of the neuromuscular synapse, the point where a nervous impulse passes from a neuron to a muscle to cause muscle movement.
In the absence of BMP signaling, their research showed, the synapse between the nerve and muscle disassembles and degenerates. This observation enabled the team to look for new genes involved in the BMP signaling system, which led to the identification of specific stabilizing factors in the nervous system.
"It is a very complicated task to keep the nervous system stable. We are using a model organism, the fruit fly, to help us rapidly identify the genetic basis for the long-term stability," Davis says. "What we have been able to do with this study is to hone in on several genes that are essential for this stability."
By examining genetic mutations that delete individual genes, the scientists were able to demonstrate that BMP signaling is required for the stability of synaptic connections. Further genetic tests demonstrated that a cytoplasmic enzyme called LIM Kinase1 is an essential link that enables BMP signaling molecules to stabilize the synapse.