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Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila

Nature Cell Biology volume 14, pages 394–400 (2012)Cite this article

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Abstract

The Drosophila lymph gland is a haematopoietic organ in which progenitor cells, which are most akin to the common myeloid progenitor in mammals, proliferate and differentiate into three types of mature cell—plasmatocytes, crystal cells and lamellocytes—the functions of which are reminiscent of mammalian myeloid cells1. During the first and early second instars of larval development, the lymph gland contains only progenitors, whereas in the third instar, a medial region of the primary lobe of the lymph gland called the medullary zone contains these progenitors2, and maturing blood cells are found juxtaposed in a peripheral region designated the cortical zone2. A third group of cells referred to as the posterior signalling centre functions as a haematopoietic niche3,4. Similarly to mammalian myeloid cells, Drosophila blood cells respond to multiple stresses including hypoxia, infection and oxidative stress5,6,7. However, how systemic signals are sensed by myeloid progenitors to regulate cell-fate determination has not been well described. Here, we show that the haematopoietic progenitors of Drosophila are direct targets of systemic (insulin) and nutritional (essential amino acid) signals, and that these systemic signals maintain the progenitors by promoting Wingless (WNT in mammals) signalling. We expect that this study will promote investigation of such possible direct signal sensing mechanisms by mammalian myeloid progenitors.

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Figure 1: Starvation induces abnormal differentiation in the lymph gland.
Figure 2: Starvation induces an inflammatory response in blood cells.
Figure 3: Systemic dilp2 is directly sensed by haematopoietic progenitors.
Figure 4: Systemic essential amino acids (EAAs) are directly sensed by haematopoietic progenitors.
Figure 5: wg as a target of Dilp2–InR–dTOR signalling.

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Acknowledgements

We thank C. J. Evans, K. T. Jones, other members of the Banerjee laboratory and J. A. Martinez-Agosto for helpful comments and discussions. We thank R. Erdmann for help with the amino-acid supplementation assay and S. Pham for confirming experiments with anti-Hml in different genetic backgrounds. We acknowledge P. Leopold, E. Hafen, E. Rulifson, L. Pick, T. P. Neufeld, R. A. Schulz, A. Courey, J-M. Reichhart, the VDRC Stock Center and the Bloomington Stock Center for fly stocks, the Developmental Studies Hybridoma Bank (University of Iowa), the Drosophila Genomics Resource Center and J. Fessler for reagents. We also thank M. Crozatiers’ group for providing the in situ hybridization protocol. This work was supported by an NIH grant (5R01 HL067395) to U.B. and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Training Grant at UCLA to J.S.

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Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA

    Jiwon Shim, Tina Mukherjee & Utpal Banerjee

  2. Molecular Biology Institute, University of California, Los Angeles, California 90095, USA

    Utpal Banerjee

  3. Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA

    Utpal Banerjee

  4. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA

    Utpal Banerjee

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  1. Jiwon Shim
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J.S designed and carried out experiments, and U.B. supervised the project. T.M. carried out experiments. J.S., T.M. and U.B. discussed and analysed results and wrote the manuscript.

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Correspondence to Utpal Banerjee.

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Shim, J., Mukherjee, T. & Banerjee, U. Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila. Nat Cell Biol 14, 394–400 (2012). https://doi.org/10.1038/ncb2453

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