The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila

Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcrip tion. During vertebrate hematopoiesis. FOG and GATA proteins cooperate to p romote erythrocyte and megakaryocyte differentiation. The Drosophila FOG ho mologue U-shaped (Ush) is expressed similarly in the blood cell anlage duri ng embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homolo gue Lozenge and Glial cells missing are required for the production of crys tal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we s how that Ush is expressed in hemocyte precursors and plasmatocytes througho ut embryogenesis and larval development, and the GATA factor Serpent is ess ential for Ush embryonic expression. Furthermore, loss of ush function resu lts in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crys tal cell production, but a mutant version of FOG-2 lacking a conserved moti f that binds the corepressor C-terminal binding protein fails to affect the cell lineage. The GATA factor Pannier (Pnr) is required for eye and heart development in Drosophila. When Ush, FOG-1, FOG-2, or mutant FOG-2 is coexp ressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr f unction. These results indicate that the fly and mouse FOG proteins functio n similarly in three distinct cellular contexts in Drosophila, but may use different mechanisms to regulate genetic events in blood vs. cardial or eye cell lineages.