Study reveals molecular mechanism of genetic variant causing mirror movement disorder

A team of Canadian and American scientists has made a promising breakthrough in understanding the origins of a mysterious neurological disorder known as mirror movements.

The discovery was made by Kaiyue Zhang, a doctoral student at the Montreal Clinical Research Institute (IRCM), affiliated with the University of Montreal, and by Karina Chaudhari, a doctoral student at the University of Pennsylvania.

As co-first authors, they published their study in the journal Scientific signage.

They were led by Frédéric Charron, professor-researcher at UdeM and director of the molecular biology of neuronal development research unit at the IRCM, in collaboration with Greg Bashaw’s team from the University of Pennsylvania.

Mirroring movement disorder is a poorly understood inherited neurological disorder that manifests itself with involuntary movements from a young age, primarily in the arms and hands.

In affected people, the right hand involuntarily reproduces the movements of the left and vice versa. This disorder can cause pain in the arms during prolonged activities and difficulty performing tasks requiring left-right coordination.

“Mirror movement disorders disrupt the daily lives of those affected,” said Charron, who is also an assistant professor at McGill University. “Simple actions like opening a water bottle can become difficult, just like playing a musical instrument.”

A flaw in a phenomenon

The cellular mechanism behind the mirror movements is a defect in a phenomenon known as axon guidance.

During embryonic development, neurons extend their axons, a long cellular cable that allows them to connect specific areas of the body together, thus establishing nerve connections.

The set of processes that control the elongation of axons and guide their navigation is called axonal guidance. Among other things, axonal guidance connects each neuron to its specific target. It is therefore crucial for the proper development of the nervous system.

Various guidance molecules direct axons toward their targets, acting as signposts to guide axons to their destinations. To do this, these guidance molecules must induce axon movement when detected by the axons.

This movement requires complex and still poorly understood molecular machinery.

In the new study, the researchers showed that the machinery necessary for guidance is actually the cytoskeleton, a microscopic skeleton that gives a cell a certain rigidity, much like the bones of the body which, through their rigidity, allow movement.

Understanding the mechanisms causing mirror movement is essential to finding ways to treat it. The Charron laboratory’s work promises new targets in this area, as well as for other diseases resulting from defects in the development of the nervous system.