A model for definitive erythropoiesis on erythroblastic islands. Erythroblasts bind to a central macrophage through the interactions of integrin-α₄β₁ on erythroblasts and Vcam1 on macrophages. Erythroblasts then undergo enucleation, in which the separation of pyrenocytes from reticulocytes may be promoted by shear stress provided by the extracellular matrix. The extracellular matrix may contribute to maintaining the close proximity of pyrenocytes and macrophages. Pyrenocytes separated from reticulocytes expose PtdSer on their surface. Protein S in the serum functions as a bridge between pyrenocytes and macrophages by binding to the PtdSer on pyrenocytes and to MerTK on macrophages, and promotes the engulfment of pyrenocytes by the macrophages.