A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors

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Abstract

The Drosophila melanogaster lymph gland is a haematopoietic organ1,2,3 in which pluripotent blood cell progenitors proliferate and mature into differentiated haemocytes. Previous work4 has defined three domains, the medullary zone, the cortical zone and the posterior signalling centre (PSC), within the developing third-instar lymph gland. The medullary zone is populated by a core of undifferentiated, slowly cycling progenitor cells, whereas mature haemocytes comprising plasmatocytes, crystal cells and lamellocytes are peripherally located in the cortical zone. The PSC comprises a third region that was first defined as a small group of cells expressing the Notch ligand Serrate5. Here we show that the PSC is specified early in the embryo by the homeotic gene Antennapedia (Antp) and expresses the signalling molecule Hedgehog. In the absence of the PSC or the Hedgehog signal, the precursor population of the medullary zone is lost because cells differentiate prematurely. We conclude that the PSC functions as a haematopoietic niche that is essential for the maintenance of blood cell precursors in Drosophila. Identification of this system allows the opportunity for genetic manipulation and direct in vivo imaging of a haematopoietic niche interacting with blood precursors.

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Figure 1: Embryonic specification of the PSC by Antp.
Figure 2: The larval PSC functions as a haematopoietic niche to maintain blood precursors in the medullary zone.
Figure 3: A Hedgehog signal from the PSC is required for the maintenance of the precursor cell population of the medullary zone.
Figure 4: PSC cells exhibit extensive processes that project into the lymph gland.

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Acknowledgements

We thank R. Cripps for drawing our attention to Antennapedia expression in the developing cardiogenic mesoderm. We thank M. Crozatier, M. Meister and A. Vincent for useful discussions. We thank all members of the Banerjee and Hartenstein laboratories for their helpful comments and suggestions. In particular, we thank S. A. Sinenko for assistance with immunohistochemistry and S.-H. Jung for her initial experiments on Hedgehog. We appreciate the help of all those who provided us with reagents: W. Gehring, S. M. Cohen, L. Cooley, K. Moses, M. Crozatier, S. Noselli, A. Salzberg, H. Müller, I. Ando, K. Basler and R. Holmgren. This work was supported by an NIH grant to U.B. and V.H., and by NIH training grant support to J.A.M.-A. and C.J.E.

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Correspondence to Utpal Banerjee.

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Mandal, L., Martinez-Agosto, J., Evans, C. et al. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors. Nature 446, 320–324 (2007) doi:10.1038/nature05585

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