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

Abstract

Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcription. During vertebrate hematopoiesis, FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation. The Drosophila FOG homologue U-shaped (Ush) is expressed similarly in the blood cell anlage during embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development, and the GATA factor Serpent is essential for Ush embryonic expression. Furthermore, loss of ush function results in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crystal cell production, but a mutant version of FOG-2 lacking a conserved motif 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 coexpressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr function. These results indicate that the fly and mouse FOG proteins function 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.

Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin

“…Amino acid substitutions in FOG-1 that impair interaction with CtBP relieve repression in reporter assays and augment blood formation in both Xenopus and Drosophila assays (52,53). Interestingly, knock-in mice that express a FOG-1 variant unable to bind CtBP are normal and fertile, and erythropoiesis at all stages of development is normal (48).…”

Drosophila Hemopoiesis and Cellular Immunity

“…This article shows that prohemocytes are bipotent progenitors. The Friend-of-GATA homolog u-shaped (ush) antagonizes crystal cell development (18) (Fig. 1A).…”

“…In Drosophila, ush is highly expressed in hemocyte precursors and throughout the development of the plasmatocyte lineage. ush is also expressed in crystal cell precursors but downregulated as these cells develop (18).…”

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles

“…Thus, FOG-1 has context-dependent activity to facilitate GATA-1 chromatin occupancy (28,29) and to restrict GATA-1 occupancy. The anti-GATA-1 activity might be related to FOG-1-mediated repression of erythropoiesis in Xenopus laevis (55) and blood cell development in Drosophila (56). The demonstration that GATA-1 target genes are differentially sensitive to the GATA-1 level͞activity emphasizes the importance of defining parameters underlying GATA factor selection of functional target sites in a genome littered with GATA motifs.…”