Disinhibition of cerebellar output by loss of restless legs syndrome-associated gene MEIS1

Genome-wide association studies have identified risk variants for restless legs syndrome (RLS), 1 , 2 , 3 , 4 , 5 , 6 but the behavioral functions and sites of action of the corresponding genes remain unknown. Here, we analyzed zebrafish mutants for candidate RLS genes and found that meis1b is required for normal locomotion behavior and cerebellar development. Neuronal manipulation experiments indicated that loss of meis1b perturbs locomotor behavior by generating abnormal cerebellar output—a mechanism reminiscent of movement disorders such as ataxia and dystonia.