Fig. 8. Model of primitive erythroid development. The changes in the signaling pathways during the first 24 hours of blast colony development are shown. Both Wnt and Numb are indicated as active in the isolated Flk1⁺ population (0 hours) as well as in the 12-hour colonies. The Notch pathway is not active in the starting Flk1 population, but is activated within the first 12 hours of colony growth. The activation of Notch induces different Wnt inhibitors, which in turn inhibits the Wnt pathway by 24 hours. Arrows below the line indicate specification to the primitive erythroid and definitive hematopoietic lineages. The thicker red arrow at 24 hours represents a higher proportion of primitive erythroid progenitors at this stage, whereas the thicker blue arrow at 48 hours depicts an expansion of the definitive lineages.