Dynamic regulation of Gata factor levels is essential for definitive erythroid development. Development of the definitive erythroid lineage is shown from progenitor cells to the terminally differentiated enucleated erythrocyte. (A) Gata 1 expression in the germline mutants used in this study. (a) Overexpression of Gata1 at late stages of development blocks terminal differentiation including enucleation. (b) In wild-type cells, Gata1 expression increases around the CFU-e/proerythroblast stage.61 (c) Low expression of Gata1 in the G1.05 mutant allows erythroid cells to develop until the proerythroblast stage. Prolonged survival of progenitors can result in a leukemic condition. (d) Gata1-null cells succumb to apoptosis at the proerythroblast stage. (B) (a) HRD-G transgenes reproduce the expression pattern of endogenous Gata1. (b and c) HRD-G transgenes rescue the G1.05 and G1KO germ line mutations, respectively. (C) (a) βLCR-G cDNA transgenes are expressed at low levels in progenitors and are sharply upregulated at late stages of development. (b) combination of the βLCR-G1 transgene with the G1.05 mutation results in partial rescue of erythroid development. (c) βLCR-G transgenes are expressed but fail to be upregulated in G1KO erythroid progenitors. Development is blocked but apoptosis is rescued. The intensity of black shading indicates protein expression levels; sloped lines indicate overexpression.
