Zebrafish as a model system to delineate the role of heme and iron metabolism during erythropoiesis

Abstract Coordination of iron acquisition and heme synthesis is required for effective erythropoiesis. The small teleost zebrafish ( Danio rerio ) is an ideal vertebrate animal model to replicate various aspects of human physiology and provides an efficient and cost-effective way to model human pathophysiology. Importantly, zebrafish erythropoiesis largely resembles mammalian erythropoiesis. Gene discovery by large-scale forward mutagenesis screening has identified key components in heme and iron metabolism. Reverse genetic screens, using morpholino-knockdown and CRISPR/Cas9, coupled with the genetic tractability of the developing embryo have further accelerated functional studies. Ultimately, the ex utero development of zebrafish embryos combined with their transparency and developmental plasticity could provide a deeper understanding of the role of iron and heme metabolism during early vertebrate embryonic development.