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.
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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.
Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.
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)
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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) doi:10.1038/nature05650
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