Ferritin is required at multiple stages during the embryonic development of Drosophila melanogaster

In Drosophila, iron is stored in the endomembrane system of cells inside a protein cavity formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. Ferritin accumulates in the midgut, nervous system, hemolymph and nephrocytes of Drosophila larvae. Here, we show that mutation of either ferritin gene product or deletion of both genes resulted in a similar set of phenotypes of embryonic lethality, ranging from non-deposition of cuticle to developmental defects associated with germ band retraction, dorsal closure and head involution. Maternal contribution of ferritin, which varied reflecting the mother’s iron stores, is used in early development, but zygotic ferritin mutants died with ectopic apoptotic events and disrupted intestinal morphology. The embryonic nervous system of ferritin mutants presented ventral nerve cord disruptions, misguided axonal projections and brain malformations. Finally, ferritin accumulation was also observed in embryonic hemocytes. One ferritin mutant showed no hemocyte ferritin accumulation and this expression was also lost by genetic inhibition of the secretory pathway. Our work suggests that insect ferritin functions in iron storage, intercellular iron transport and protection from oxidative stress at multiple times during the embryonic development of Drosophila melanogaster.