The most prevalent nutrient deficiency in the world is a lack of iron. It has been estimated that 35 to 58% of women have some degree of iron deficiency. The occurrence of iron deficiency is particularly prevalent during pregnancy. It has been reported that for children under 2 years of age, the estimated prevalence of iron deficiency is 25%. While it is known that iron deficiency in children is associated with a number of neural defects including behavioral effects, alterations to the blood brain barrier, changes in fatty acid composition, and hypo-myelination, the cellular mechanisms leading to such defects are not well understood. For example, it has been hypothesized that iron deficiency leads to a failure of oligodendrocyte maturation or survival. Another possibility that has been discussed is a failure in the generation of oligodendrocytes from the precursor cells that give rise to them due to iron deficiency. These hypotheses are based on observations that there is a peak of iron availability in vivo that coincides precisely with peak periods of myelination and that normal myelination does not occur in the absence of sufficient iron. The vast majority of studies that try to decipher the specific role of iron in gliogenesis have focused on the postnatal stage of development, when oligodendrocytes form functional myelin in vivo. Our own studies, however, have indicated that a lack of iron has a severe impact on the very early glial precursor cells of the embryonic spinal cord. Embryonic glial precursor cells that grow in low iron seem to be impaired in their ability to divide and to differentiate. Thus, we now propose that the hypomyelination that is associated with iron deficiency is likely to be a late consequence of damage that occurred already during embryogenesis. We propose that iron interferes with the earliest developmental steps ancestral to oligodendrocyte generation and therefore disrupts the normal sequence of progressive lineage restriction that is required for proper generation of these myelin-producing cells.
