The Friend of GATA protein U-shaped functions as a hematopoietic tumor suppressor in Drosophila

Abstract

Drosophila has emerged as an important model system to discover and analyze genes controlling hematopoiesis. One regulatory network known to control hemocyte differentiation is the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signal-transduction pathway. A constitutive activation mutation of the Janus kinase Hopscotch (hopscotch(Tumorous-lethal); hop(Tum-l)) results in a leukemia-like over-proliferation of hemocytes and copious differentiation of lamellocytes during larval stages. Here we show that the Friend of GATA (FOG) protein U-shaped (Ush) is expressed in circulating and lymph gland hemocytes, where it plays a critical role in controlling blood cell proliferation and differentiation. Our findings demonstrate that a reduction in ush function results in hematopoietic phenotypes strikingly similar to those observed in hop(Tum-l) animals. These include lymph gland hypertrophy, increased circulating hemocyte concentration, and abundant production of lamellocytes. Forced expression of N-terminal truncated versions of Ush likewise leads to larvae with severe hematopoietic anomalies. In contrast, expression of wild-type Ush results in a strong suppression of hop(Tum-l) phenotypes. Taken together, our findings demonstrate that U-shaped acts to control larval hemocyte proliferation and suppress lamellocyte differentiation, likely regulating hematopoietic events downstream of Hop kinase activity. Such functions appear to be facilitated through Ush interaction with the hematopoietic GATA factor Serpent (Srp).

Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

“…Akt1 04226 is a lacZ enhancer trap creating an Akt1 hypomorphic allele (42). eater-GFP (*30, II) and eater-Gal4 (*217D201, II) were from T. Tokusumi (University of Notre Dame, Notre Dame, IN) (15,21). Gli-Gal4 (18,22), from M. Stern (Rice University, Houston, TX), drives expression in perineurial glia (43,44).…”

“…1 C and G). By expression of the plasmatocyte-specific marker eater-GFP, the attached cells were identified as plasmatocytes, a macrophage-like cell type normally circulating in the hemolymph (15) (Fig. 1 D and D′).…”

U-shaped Gene Induced by Ecdysone Signal Pathway in Drosophila

“…The ush gene belong to FOG family, the current studies found that all the FOG members function depends on the GATA transcription factors [3]. The ush can also interact with the srp to mediate the insect hemocytes differentiation [14,15]. In this study, we found that the ush gene not only express during molting and metamorphosis when hemocytes undergo differentiation, but the ush gene also express during feed stage.…”

“…Although the specific role of ush on larvae hemocytes differentiation is still unclear, but the knockdown of ush gene resulting in the destruction of drosophila hemocytes differentiation [15]. This results suggest that ush play an important role in larval hemocytes development.…”

“…During the larval stage, ush gene only express during third instar larvae [6]. After Drosophia ush gene was knocked down, the Drosophia lamellocytes number in lymph gland increased significantly, caused lymph gland enlargement, those results indicate that ush can suppress lamellocytes differentiate into other hemocytes [7]. The ush gene mainly express in drosophila plasmatocytes, and may be associated with the maintenance of plasmatocytes function [8].…”