To define the importance of iron storage in oligodendrocyte development and function, the ferritin heavy subunit (Fth) was specifically deleted in oligodendroglial cells. Blocking Fth synthesis in Sox10 or NG2-positive oligodendrocytes during the first or the third postnatal week significantly reduces oligodendrocyte iron storage and maturation. The brain of Fth KO animals presented an important decrease in the expression of myelin proteins and a substantial reduction in the percentage of myelinated axons. This hypomyelination was accompanied by a decline in the number of myelinating oligodendrocytes and with a reduction in proliferating oligodendrocyte progenitor cells (OPCs). Importantly, deleting Fth in Sox10-positive oligodendroglial cells after postnatal day 60 has no effect on myelin production and/or oligodendrocyte quantities. We also tested the capacity of Fth-deficient OPCs to remyelinate the adult brain in the cuprizone model of myelin injury and repair. Fth deletion in NG2-positive OPCs signifi...