Regulation of erythroid development by iron metabolism

Erythropoiesis is a highly complex process involving a highly coordinated set of cellular processes, culminating with extrusion of the nucleus resulting in formation of a mature erythrocyte. The main function of erythroid cells is to synthesize hemoglobin, which utilizes most of the iron in the body. As such, erythropoiesis is a key driver of systemic iron metabolism. Iron metabolism also plays a central role in erythropoietic development and is essential for processes such as proliferation, cytoskeletal remodeling and nuclear condensation that are required for erythropoietic development. As such, defects in iron metabolism cause a wide range of developmental defects in vertebrate models of hematopoiesis. Recent studies have uncovered a treasure trove of mechanisms by which iron sensing and utilization interacts with the erythroid developmental process. This chapter surveys the mechanisms by which iron metabolism facilitates terminal erythroid differentiation and suggests areas for further investigation based on studies of iron-dependent pathways in non-erythroid cells.