Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency

Abstract

Studies using Drosophilamelanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss- and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.

ACKNOWLEDGMENTS

This work was supported by Public Health Service grant DK072229 from the National Institutes of Health.

We gratefully acknowledge our colleagues for providing fly strains and antibodies. R. A. Schulz and R. P. Sorrentino provided y¹w; ush^vx22/CyO, y⁺ and y¹w; ush^r24/CyO, y⁺ stocks. M. P. Zeidler and J. C. Hombria provided domeMESO strains w; domeMESO/CyO and w p{w⁺, dome-MESO}BN1. D. J. Montell provided the FRT 82b, e, ca stat^397-6/TM3 stock. Istavan Ando provided the P1, L1, and He antibodies. F. C. Kafatos provided the ProPO antibody. We also thank Noam Broder for excellent technical assistance. We are grateful to T. Antalis, S. DasSharma, and A. Keegan for critical comments.