Drosophila immune response involves three types of hemocytes (‘blood cells’). One cell type, the lamellocyte, is induced to differentiate only under particular conditions, such as parasitization by wasps. Here, we have investigated the mechanisms underlying the specification of lamellocytes. We first show that collier (col), the Drosophila orthologue of the vertebrate gene encoding early B-cell factor (EBF), is expressed very early during ontogeny of the lymph gland, the larval hematopoietic organ. In this organ, Col expression prefigures a specific posterior region recently proposed to act as a signalling centre, the posterior signalling centre (PSC). The complete lack of lamellocytes in parasitized col mutant larvae revealed the critical requirement for Col activity in specification of this cell type. In wild-type larvae, Col expression remains restricted to the PSC following parasitization, despite the massive production of lamellocytes. We therefore propose that Col endows PSC cells with the capacity to relay an instructive signal that orients hematopoietic precursors towards the lamellocyte fate in response to parasitization. Considered together with the role of EBF in lymphopoiesis, these findings suggest new parallels in cellular immunity between Drosophila and vertebrates. Further investigations on Col/EBF expression and function in other phyla should provide fresh insight into the evolutionary origin of lymphoid cells.
References
[1]
Asha H, Nagy I, Kovacs G, Stetson D, Ando I, et al. (2003) Analysis of ras-induced overproliferation in Drosophila hemocytes. Genetics 163: 203–215.
[2]
Bachmann A, Knust E (1998) Dissection of cis-regulatory elements of the Drosophila gene Serrate. Dev Genes Evol 208: 346–351.
[3]
Braun A, Lemaitre B, Lanot R, Zachary D, Meister M (1997) Drosophila immunity: Analysis of larval hemocytes by P-element-mediated enhancer trap. Genetics 147: 623–634.
[4]
Campos-Ortega JA, Hartenstein V (1997) The embryonic development of . Berlin: Springer. 405 p.
[5]
Crozatier M, Vincent A (1999) Requirement for the Drosophila COE transcription factor Collier in formation of an embryonic muscle: Transcriptional response to Notch signalling. Development 126: 1495–1504.
[6]
Crozatier M, Valle D, Dubois L, Ibnsouda S, Vincent A (1996) Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain. Curr Biol 6: 707–718.
[7]
Crozatier M, Valle D, Dubois L, Ibnsouda S, Vincent A (1999) Head versus trunk patterning in the Drosophila embryo; collier requirement for formation of the intercalary segment. Development 126: 4385–4394.
[8]
Duvic B, Hoffmann JA, Meister M, Royet J (2002) Notch signaling controls lineage specification during Drosophila larval hematopoiesis. Curr Biol 12: 1923–1927.
[9]
Evans CJ, Hartenstein V, Banerjee U (2003) Thicker than blood: Conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev Cell 5: 673–690.
[10]
Goto A, Kadowaki T, Kitagawa Y (2003) Drosophila hemolectin gene is expressed in embryonic and larval hemocytes and its knock down causes bleeding defects. Dev Biol 264: 582–591.
[11]
Hagman J, Belanger C, Travis A, Turck CW, Grosschedl R (1993) Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dev 7: 760–773.
[12]
Harrison DA, Binari R, Stines Nahreini T, Gilman M, Perrimon N (1995) Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J 14: 2857–2865.
[13]
Holz A, Bossinger B, Strasser T, Janning W, Klapper R (2003) The two origins of hemocytes in Drosophila. Development 130: 4955–4962.
[14]
Hou XS, Perrimon N (1997) The JAK-STAT pathway in Drosophila. Trends Genet 13: 105–110.
[15]
Kambris Z, Hoffmann JA, Imler JL, Capovilla M (2002) Tissue and stage-specific expression of the Tolls in Drosophila embryos. Gene Expr Patterns 2: 311–317.
[16]
Kimbrell DA, Beutler B (2001) The evolution and genetics of innate immunity. Nat Rev Genet 2: 256–267.
[17]
Lanot R, Zachary D, Holder F, Meister M (2001) Postembryonic hematopoiesis in Drosophila. Dev Biol 230: 243–257.
[18]
Lebestky T, Chang T, Hartenstein V, Banerjee U (2000) Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288: 146–149.
[19]
Lebestky T, Jung SH, Banerjee U (2003) A Serrate-expressing signaling center controls Drosophila hematopoiesis. Genes Dev 17: 348–353.
[20]
Lin H, Grosschedl R (1995) Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376: 263–267.
[21]
Luo H, Hanratty WP, Dearolf CR (1995) An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia-like hematopoietic defects. EMBO J 14: 1412–1420.
[22]
Maier H, Hagman J (2002) Roles of EBF and Pax-5 in B lineage commitment and development. Semin Immunol 14: 415–422.
[23]
Mayer WE, Uinuk-Ool T, Tichy H, Gartland LA, Klein J, et al. (2002) Isolation and characterization of lymphocyte-like cells from a lamprey. Proc Natl Acad Sci U S A 99: 14350–14355.
[24]
Meister M (2004) Blood cells of Drosophila Cell lineages and role in host defence. Curr Opin Immunol 16: 10–15.
[25]
Mikkola I, Heavey B, Horcher M, Busslinger M (2002) Reversion of B cell commitment upon loss of Pax5 expression. Science 297: 110–113.
[26]
Nutt SL, Heavey B, Rolink AG, Busslinger M (1999) Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401: 556–562.
[27]
Orkin SH (2000) Diversification of haematopoietic stem cells to specific lineages. Nat Rev Genet 1: 57–64.
[28]
Qiu P, Pan PC, Govind S (1998) A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development 125: 1909–1920.
[29]
Rehorn KP, Thelen H, Michelson AM, Reuter R (1996) A molecular aspect of hematopoiesis and endoderm development common to vertebrates and Drosophila. Development 122: 4023–4031.
[30]
Rizki TM, Rizki RM (1984) The cellular defense system of . In: King RC, Akai H, editors. Insect ultrastructure. New York: Plenum Publishing. pp. 579–604.
[31]
Rolink AG, Nutt SL, Melchers F, Busslinger M (1999) Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 401: 603–606.
[32]
Russo J, Dupas S, Frey F, Carton Y, Brehelin M (1996) Insect immunity: Early events in the encapsulation process of parasitoid (Leptopilina boulardi) eggs in resistant and susceptible strains of Drosophila. Parasitology 112: 135–142.
[33]
Schebesta M, Heavey B, Busslinger M (2002) Transcriptional control of B-cell development. Curr Opin Immunol 14: 216–223.
[34]
Schubiger M, Palka J (1987) Changing spatial patterns of DNA replication in the developing wing of Drosophila. Dev Biol 123: 145–153.
[35]
Shrestha R, Gateff E (1982) Ultrastructure and cytochemistry of the cell types in the larval hematopoietic organs and hemolymph of . Dev Growth Differ 24: 65–82.
[36]
Sorrentino RP, Carton Y, Govind S (2002) Cellular immune response to parasite infection in the Drosophila lymph gland is developmentally regulated. Dev Biol 243: 65–80.
[37]
Sparrow JC (1978) Melanotic tumours. In: Ashburner M, Wright TRF, editors. The genetics and biology of Drosophila. London: Academic Press. pp. 277–315.
[38]
Tepass U, Fessler LI, Aziz A, Hartenstein V (1994) Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development 120: 1829–1837.
[39]
Waltzer L, Ferjoux G, Bataille L, Haenlin M (2003) Cooperation between the GATA and RUNX factors Serpent and Lozenge during Drosophila hematopoiesis. EMBO J 22: 6516–6525.
[40]
Ward EJ, Skeath JB (2000) Characterization of a novel subset of cardiac cells and their progenitors in the Drosophila embryo. Development 127: 4959–4969.
[41]
Warren LA, Rothenberg EV (2003) Regulatory coding of lymphoid lineage choice by hematopoietic transcription factors. Curr Opin Immunol 15: 166–175.
