Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre

Abstract

Drosophila haemocytes (blood cells) originate from a specialized haematopoietic organ—the lymph gland. Larval haematopoietic progenitors (prohaemocytes) give rise to three types of circulating haemocytes: plasmatocytes, crystal cells and lamellocytes. Lamellocytes, which are devoted to encapsulation of large foreign bodies, only differentiate in response to specific immune threats, such as parasitization by wasps. Here we show that a small cluster of signalling cells, termed the PSC (posterior signalling centre)1, controls the balance between multipotent prohaemocytes and differentiating haemocytes, and is necessary for the massive differentiation of lamellocytes that follows parasitization. Communication between the PSC and haematopoietic progenitors strictly depends on the PSC-restricted expression of Collier, the Drosophila orthologue of mammalian early B-cell factor. PSC cells act, in a non-cell-autonomous manner, to maintain JAK/STAT signalling activity in prohaemocytes, preventing their premature differentiation. Serrate-mediated Notch signalling from the PSC is required to maintain normal levels of col transcription. The key role of the PSC in controlling blood cell homeostasis is reminiscent of interactions between haematopoietic progenitors and their micro-environment in vertebrates2,3,4, thus further highlighting the interest of Drosophila as a model system for studying the evolution of haematopoiesis and cellular innate immunity.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The PSC is required to maintain a pool of haematopoietic progenitors.
Figure 2: JAK/STAT signalling pathway is required to maintain a pool of prohaemocytes in the lymph gland.
Figure 3: Premature differentiation of prohaemocytes into lamellocytes on wasp infestation.

Similar content being viewed by others

References

  1. Lebestky, T., Jung, S. H. & Banerjee, U. A Serrate-expressing signaling center controls Drosophila hematopoiesis. Genes Dev. 17, 348–353 (2003)

    Article  CAS  Google Scholar 

  2. Nagasawa, T. Microenvironmental niches in the bone marrow required for B-cell development. Nature Rev. Immunol. 6, 107–116 (2006)

    Article  CAS  Google Scholar 

  3. Wilson, A. & Trumpp, A. Bone-marrow haematopoietic-stem-cell niches. Nature Rev. Immunol. 6, 93–106 (2006)

    Article  CAS  Google Scholar 

  4. Scadden, D. T. The stem-cell niche as an entity of action. Nature 441, 1075–1079 (2006)

    Article  ADS  CAS  Google Scholar 

  5. Holz, A., Bossinger, B., Strasser, T., Janning, W. & Klapper, R. The two origins of haemocytes in Drosophila. Development 130, 4955–4962 (2003)

    Article  CAS  Google Scholar 

  6. Bataille, L., Auge, B., Ferjoux, G., Haenlin, M. & Waltzer, L. Resolving embryonic blood cell fate choice in Drosophila: interplay of GCM and RUNX factors. Development 132, 4635–4644 (2005)

    Article  CAS  Google Scholar 

  7. Rizki, R. M. & Rizki, T. M. Selective destruction of a host blood cell type by a parasitoid wasp. Proc. Natl Acad. Sci. USA 81, 6154–6158 (1984)

    Article  ADS  CAS  Google Scholar 

  8. Lanot, R., Zachary, D., Holder, F. & Meister, M. Postembryonic hematopoiesis in Drosophila. Dev. Biol. 230, 243–257 (2001)

    Article  CAS  Google Scholar 

  9. Evans, C. J., Hartenstein, V. & Banerjee, U. Thicker than blood: conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev. Cell 5, 673–690 (2003)

    Article  CAS  Google Scholar 

  10. Meister, M. & Lagueux, M. Drosophila blood cells. Cell. Microbiol. 5, 573–580 (2003)

    Article  CAS  Google Scholar 

  11. Jung, S. H., Evans, C. J., Uemura, C. & Banerjee, U. The Drosophila lymph gland as a developmental model of hematopoiesis. Development 132, 2521–2533 (2005)

    Article  CAS  Google Scholar 

  12. Crozatier, M., Ubeda, J. M., Vincent, A. & Meister, M. Cellular immune response to parasitization in Drosophila requires the EBF orthologue Collier. PLoS Biol. 2, E196 (2004)

    Article  Google Scholar 

  13. Irving, P. et al. New insights into Drosophila larval haemocyte functions through genome-wide analysis. Cell. Microbiol. 7, 335–350 (2005)

    Article  CAS  Google Scholar 

  14. Sun, X. & Artavanis-Tsakonas, S. The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands. Development 122, 2465–2474 (1996)

    CAS  PubMed  Google Scholar 

  15. De Joussineau, C. et al. Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila. Nature 426, 555–559 (2003)

    Article  ADS  CAS  Google Scholar 

  16. Spradling, A., Drummond-Barbosa, D. & Kai, T. Stem cells find their niche. Nature 414, 98–104 (2001)

    Article  ADS  CAS  Google Scholar 

  17. Hombria, J. C., Brown, S., Hader, S. & Zeidler, M. P. Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. Dev. Biol. 288, 420–433 (2005)

    Article  CAS  Google Scholar 

  18. Arbouzova, N. I. & Zeidler, M. P. JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 133, 2605–2616 (2006)

    Article  CAS  Google Scholar 

  19. Kraaijeveld, A. R. & Godfray, H. C. Trade-off between parasitoid resistance and larval competitive ability in Drosophila melanogaster. Nature 389, 278–280 (1997)

    Article  ADS  CAS  Google Scholar 

  20. Rolff, J. & Siva-Jothy, M. T. Invertebrate ecological immunology. Science 301, 472–475 (2003)

    Article  ADS  CAS  Google Scholar 

  21. Decotto, E. & Spradling, A. C. The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. Dev. Cell 9, 501–510 (2005)

    Article  CAS  Google Scholar 

  22. Lin, H. The stem-cell niche theory: lessons from flies. Nature Rev. Genet. 3, 931–940 (2002)

    Article  CAS  Google Scholar 

  23. Kimble, J. & Crittenden, S. L. Germline proliferation and its control. In WormBook (eds The C. elegans Research Community), doi/10.1895/worm-book.1.13.1 (15 August, 2005)

    Google Scholar 

  24. Calvi, L. M. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425, 841–846 (2003)

    Article  ADS  CAS  Google Scholar 

  25. Zhang, J. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836–841 (2003)

    Article  ADS  CAS  Google Scholar 

  26. Sepp, K. J. & Auld, V. J. Conversion of lacZ enhancer trap lines to GAL4 lines using targeted transposition in Drosophila melanogaster. Genetics 151, 1093–1101 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Bourbon, H. M. et al. A P-insertion screen identifying novel X-linked essential genes in Drosophila. Mech. Dev. 110, 71–83 (2002)

    Article  CAS  Google Scholar 

  28. Crozatier, M. & Vincent, A. Requirement for the Drosophila COE transcription factor Collier in formation of an embryonic muscle: transcriptional response to Notch signalling. Development 126, 1495–1504 (1999)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J. Castelli-Gair Hombria, O. Devergne, M. Milan, S. Noselli, M. Zeidler and the Bloomington Stock Center for fly stocks, I. Ando and H. M. Müller for antibodies, and M. Haenlin, J. Smith, L. Waltzer for critical reading of the manuscript and discussion. We are grateful to platforme Toulouse RIO imaging and B. Ronsin for assistance with confocal microscopy. This work was supported by CNRS, a European Marie Curie PhD Training programme grant and Ministère de la Recherche et de la technologie (ACI Biologie Cellulaire, Moléculaire et Structurale) et Ministère des affaires étrangères (Programme Egide).

Author Contributions J.K., M.M., A.V. and M.C. conceived the experiments, which were essentially performed by J.K. and M.C. L.D. and M.M. provided crucial reagents. R.M. assisted with experiments involving wasp infestation. A.V. and M.C. wrote the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michèle Crozatier.

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1- S3 with Legends. Fig. S1 illustrates PSC-specific expression driven by Pcol85-Gal4. Forced expression of the apoptosis inducing gene reaper in the PSC leads to death of the PSC cells. Fig. S2 illustrates PSC cells extend filopodia. Fig.S3 illustrates loss of col activity in the PSC does not affect the formation of the medullary zone in the second instar larvae. (PDF 258 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krzemień, J., Dubois, L., Makki, R. et al. Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre. Nature 446, 325–328 (2007). https://doi.org/10.1038/nature05650

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05650

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing