Taken together these findings show species conservation of the defining physiological properties of oligodendrocyte‐lineage cells and crucially establish a platform to investigate disease related changes. Here, we examined the development and maturation of mutant C9ORF72‐patient derived OPCs given the accumulating evidence implicating oligodendrocyte dysfunction and pathology in sporadic and familial ALS including impaired maturation of oligodendrocytes in a mSOD1 mouse model 3, 4, 5, 61. Furthermore, the C9ORF72 hexanucleotide expansion is implicated as a causal factor in abnormal neuronal excitability 47 and recent studies indicate that nuclear‐cytoplasmic transport is affected in motorneurons 62, 63. The precise function of C9ORF72 protein remains unknown although accumulating evidence implicates a gain of function mediated toxicity. This includes the absence of survival or motor deficits in a C9orf72 knock‐out mouse model and a number of studies showing direct toxicity of RNA or translated dipeptide products 62, 63, 64.
