# Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development

## TL;DR

This study shows that ferritin is essential in multiple tissues during fruit fly development, playing roles in iron storage, transport, and protection against oxidative stress.

## Contribution

The study reveals ferritin's multifunctional role in iron management and tissue development in Drosophila embryos.

## Key findings

- Ferritin mutations cause cuticular and nervous system defects in Drosophila embryos.
- Ferritin is involved in iron storage, transport, and protection from oxidative stress.
- Maternal ferritin contributes to early embryonic development based on the mother's iron stores.

## Abstract

In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother’s iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.