Grant: Project Grant

Lateralization of motor control refers to the ability to perform movements on only one side of the body and is essential for activities such as coordinated hand movements and walking. Lateralization of motor control depends on the correct communication between the right and left sides of the nervous system through crossing nerve fibres. Defective lateralized motor control can result in mirror movements (MM), where voluntary movements on one side of the body are mirrored by involuntary movements on the opposite side of the body. In 2010, we reported that MM can result from mutations in DCC, a gene critical in guiding developing axons (long extensions of nerve cells) to the nervous system midline. We have assembled the world's largest cohort of MM individuals. About one-third carry mutations in DCC and two-thirds are genetically unexplained, suggesting that many more MM genes remain to be discovered. Our unique MM cohort provides an exceptional opportunity to study the physiological, molecular and genetic mechanisms underlying lateralization of motor control, and how this is altered in MM. In this research project, we will identify novel genes important for the lateralization of motor control by genetically studying our MM cohort. In addition, we will functionally assess the role of the novel MM gene mutations using in vitro and mouse experiments. We hypothesize that the majority of novel genes will have a role in midline axon guidance and DCC signaling. This study will identify novel MM genes and expand our understanding of the physiological and molecular basis of lateralization of motor control, axon guidance and circuit formation.