Developing organs require iron for a myriad of functions, but embryos deleted of the
major adult transport proteins, transferrin or its receptor transferrin receptor1
(TfR1(-/-)), still initiate organogenesis, suggesting that non-transferrin pathways
are important. To examine these pathways, we developed chimeras composed of fluorescence-tagged
TfR1(-/-) cells and untagged wild-type cells. In the kidney, TfR1(-/-) cells populated
capsule and stroma, mesenchyme and nephron, but were underrepresented in ureteric
bud tips. Consistently, TfR1 provided transferrin to the ureteric bud, but not to
the capsule or the stroma. Instead of transferrin, we found that the capsule internalized
ferritin. Since the capsule expressed a novel receptor called Scara5, we tested its
role in ferritin uptake and found that Scara5 bound serum ferritin and then stimulated
its endocytosis from the cell surface with consequent iron delivery. These data implicate
cell type-specific mechanisms of iron traffic in organogenesis, which alternatively
utilize transferrin or non-transferrin iron delivery pathways.