FAILURE OF MEGAKARYOPOIESIS AND ARRESTED ERYTHROPOIESIS IN MICE LACKING THE GATA-1 TRANSCRIPTIONAL COFACTOR FOG

GATA transcription factors are required for the differentiation of div erse cell types in several species. Recent evidence suggests that thei r biologic activities may be modulated through interaction with multit ype zinc finger proteins, such as Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG; cooperates with the hematopoietic transcr iption faster GATA-1 to promote erythroid and megakaryocytic different iation. We show here that mice lacking FOG die during mid-embryonic de velopment With severe anemia. FOG(-/-) erythroid cells display a marke d, But partial, blockage of maturation, reminiscent of GATA-1(-) eryth roid precursors. In contrast to GATA-1 deficiency, however, megakaryoc ytes fail to develop in the absence of FOG. Although the FOG(-/-) eryt hroid phenotype supports the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points to a pivotal, GATA-1-independent r equirement Ear FOG in megakaryocyte development from the bipotential e rythroid/megakaryocytic progenitor. We speculate that FOG and other FO G-like proteins serve as complex cofactors that act through both GATA- dependent and GATA-independent mechanisms.