An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells

GATA-1 is a tissue-specific transcription factor that is essential for the production of red blood cells(1,2). Here we show that overexpression of GAT A-1 in erythroid cells inhibits their differentiation, leading to a lethal anaemia. Using chromosome-X-inactivation of a GATA-1 transgene and chimaeri c animals, we show that this defect is intrinsic to erythroid cells, but ne vertheless cell nonautonomous. Usually, cell nonautonomy is thought to refl ect aberrant gene function in cells other than those that exhibit the pheno type(3). On the basis of our data, we propose an alternative mechanism in w hich a signal originating from wild-type erythroid cells restores normal di fferentiation to cells overexpressing GATA-1 in vivo. The existence of such a signalling mechanism indicates that previous interpretations of cell-non autonomous defects may be erroneous in some cases and may in fact assign ge ne function to incorrect cell types.