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 Université de Montréal, and by Karina Chaudhari, a doctoral student at the University of Pennsylvania.
As co-first authors, they published their study today in the journal Science Signaling.
They were led by Frédéric Charron, an UdeM research professor and director of the IRCM's molecular biology of neuronal development research unit, in collaboration with Greg Bashaw's team at the University of Pennsylvania.
Mirror movement disorder is a poorly understood hereditary neurological disorder that manifests itself in involuntary movements from an early age, mainly in the arms and hands.
In those affected, the right hand involuntarily reproduces the movements of the left and vice versa. The disorder can cause pain in the arms during prolonged activities, and difficulties in performing tasks requiring left-right coordination.
"Mirror movement disorder disrupts the daily lives of affected individuals," said Charron, who's also an adjunct professor at McGill University. "Simple actions such as opening a bottle of water can become difficult, as can playing a musical instrument."
A defect in a phenomenon
The cellular mechanism behind mirror movements is a defect in a phenomenon known as axon guidance.
During embryonic development, neurons extend their axons, a long cellular cable that enables them to link specific areas of the body together, thus establishing nerve connections.
The set of processes that control axon elongation and guide its navigation is called axon guidance. Among other things, axon guidance connects each neuron to its specific target. It is therefore crucial to the proper development of the nervous system.
Various guidance molecules direct axons to their targets, acting like signposts to guide axons to their destination. To do this, these guidance molecules must induce axon movement when they are detected by axons.
This movement requires a complex molecular machinery that is still poorly understood.
In the new study, the researchers showed that the machinery required for guidance is in fact the cytoskeleton, a microscopic skeleton which gives a cell a certain rigidity, rather like the bones of the body which, through their rigidity, enable movement.
Understanding the mechanisms causing mirror movement is key to finding ways to treat it. The work of the Charron laboratory promises new targets in that regard, as well as for other diseases resulting from defects in the development of the nervous system.
About this study
"A human DCC variant causing mirror movement disorder reveals that the WAVE regulatory complex mediates axon guidance by netrin-1-DCC," by Kaiyue Zhang, Karina Chaudhari et. al, was published Oct. 1, 2024 in Science Signaling. The research teams of Myriam Srour of the Montreal Children's Hospital, Junmei Wang of the University of Pittsburgh, and Baoyu Chen of Iowa State University also contributed to this work. Funding was provided by the Canadian Institutes of Health Research (CIHR), the Neurobasis project of the Canada Foundation for Innovation (CFI), the Fonds de recherche du Québec - Santé (FRQS), the China Scholarship Council (CSC), the National Science Foundation (NSF), and the National Institutes of Health (NIH). Frédéric Charron holds the Canada Research Chair in Developmental Neurobiology.
