Regular articleTranscriptional regulation of hematopoiesis in Drosophila
Introduction
Recent investigations have determined that several factors important for hematopoiesis in vertebrates are also functionally conserved in Drosophila. In vertebrate hematopoiesis, a common progenitor cell gives rise to all blood cell lineages [1]. Differentiating progenitors then take on either a lymphoid or myeloid cell fate, which then limits lineage commitment to any fate within a particular subgroup. The lymphoid progenitors give rise to B and T lymphocytes, while myeloid progenitors give rise to many cell types including erythrocytes and monocytes [1]. Although distinct, Drosophila blood cells most closely resemble cells of the vertebrate myeloid lineage, particularly monocyte/macrophages and granulocytes. This distinction is based upon both morphological and functional similarities, including phagocytic and immune-related activities. As will be described further below, Drosophila blood cells are similar to those of vertebrates not only in terms of functionality but also in terms of a genetic hierarchy directing hematopoietic differentiation. This review describes the Drosophila blood cell lineages and what is known about the transcriptional regulators that lead to their specification and differentiation.
Section snippets
Hemocyte cell types
In Drosophila, blood cells are referred to as hemocytes, of which there are at least three terminally differentiated types: plasmatocytes, crystal cells, and lamellocytes. Plasmatocytes are the predominant cell type at all developmental stages and represent approximately 95% of all hemocytes, with crystal cells making up the majority of the remainder [2]. Lamellocytes are produced in very small numbers, if at all, under normal conditions, but can be induced in large numbers under conditions of
Origins of Drosophila hemocytes
In the embryo, both plasmatocytes and crystal cells are derived from a precursor population located in the procephalic mesoderm, first observable in around stage 5 [6], [18]. The hematopoietic precursors (prohemocytes) express the GATA transcription factor Serpent (Srp), which is required for hematopoiesis in Drosophila [18], [19]. As these cells begin to differentiate, plasmatocyte precursors initiate expression of the transcription factor Gcm (glial cells missing) [20] and begin to migrate
Transcriptional regulation during hematopoiesis
The transcription factor Serpent (Srp) is expressed in all hemocyte precursors and is required for hematopoietic development [18], [19]. Serpent is a member (one of five in Drosophila) of the highly conserved GATA family of zinc-finger transcription factors that recognize the consensus DNA binding site WGATAR [24]. All vertebrate GATA factors contain two zinc finger motifs of the Cys-X2-Cys-X17-Cys-X2-Cys type separated by 29 amino acids; the amino-proximal zinc finger is often referred to as
References (47)
- et al.
Postembryonic hematopoiesis in Drosophila
Dev. Biol.
(2001) - et al.
Cellular immune response to parasite infection in the Drosophila lymph gland is developmentally regulated
Dev. Biol.
(2002) - et al.
Ultrastructure and cytochemistry of the tumorous blood cells in the mutant lethal(3)malignant blood neoplasm of Drosophila melanogaster
J. Invert. Pathol.
(1986) - et al.
Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells
Immunity
(1996) - et al.
Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression
Insect Biochem. Mol. Biol.
(1997) - et al.
How Drosophila combats microbial infectiona model to study innate immunity and host-pathogen interactions
Curr. Opin. Microbiol.
(2002) - et al.
JNK signaling pathway is required for efficient wound healing in Drosophila
Dev. Biol.
(2002) - et al.
Role of the prophenoloxidase-activating system in invertebrate immunity
Curr. Opin. Immunol.
(1998) - et al.
Lamellocyte differentiation in Drosophila larvae parasitized by Leptopilina
Dev. Comp. Immunol.
(1992) - et al.
Walking the walkmigration and other common themes in blood and vascular development
Cell
(2002)
Interactions between the cellular and humoral immune responses in Drosophila
Curr. Biol.
Functional conservation of hematopoietic factors in Drosophila and vertebrates
Differentiation
Function of CBFbeta/Bro proteins
Semin. Cell Dev. Biol.
The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo
Cell
Glial cells missinga binary switch between neuronal and glial determination in Drosophila
Cell
Glial cells missinga genetic switch that controls glial versus neuronal fate
Cell
gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila
Dev. Biol.
Fruit fly “leukemia,”
Biochim. Biophys. Acta
Diversification of haematopoietic stem cells to specific lineages
Nature Rev. Genet.
The circulatory system and associated cells and tissues
Embryonic origin of hemocytes and their relationship to cell death in Drosophila
Development
Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila
Science
Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli
Nature
Cited by (40)
GATA binding protein 6 regulates apoptosis in silkworms through interaction with poly (ADP-ribose) polymerase
2024, International Journal of Biological MacromoleculesProteomics of purified lamellocytes from Drosophila melanogaster HopT<sup>um-l</sup> identifies new membrane proteins and networks involved in their functions
2021, Insect Biochemistry and Molecular BiologyCitation Excerpt :Crystal cells represent the remaining 5% of hemocytes; these non-phagocytic cells contain tyrosine-rich crystalline inclusions and two prophenoloxidases (PPO1 and PPO2) involved in various melanization processes (Rizki and Rizki, 1959; Bidla et al., 2007; Dudzic et al., 2015). Under stress, crystal cells lyse and release the two pro-enzymes that are activated by proteolysis to produce different quinone derivatives from tyrosine that ultimately generate the black melanin involved in clot formation during wound healing or nodulation (Cerenius and Söderhäll, 2011; Evans and Banerjee, 2003). Under healthy conditions, very few lamellocytes circulate but their numbers increase sharply in the fly larva after infestation by Hymenoptera endoparasitoid wasps (Banerjee et al., 2019; Russo et al., 2001; Rizki and Rizki, 1992; Carton et al., 2008).
Interaction of entomopathogenic fungi with the host immune system
2018, Developmental and Comparative ImmunologyCitation Excerpt :Insect cellular immune responses rely on the circulating hemocytes, which are divided into different types based on morphological characteristics and functional features (Price and Ratcliffe, 1974). In Drosophila, there are at least three differentiated hemocyte types: plasmatocytes, crystal cells, and lamellocytes (Evans and Banerjee, 2003; Hartenstein, 2006; Lanot et al., 2001; Lemaitre et al., 1996). Insect hemocytes are involved in a series of cellular defenses including nodulation, phagocytosis, and encapsulation (Michael, 2008).
Insect Immunity to Entomopathogenic Fungi
2016, Advances in GeneticsCitation Excerpt :Phagocytosis involves extensive membrane reorganization, cytoskeletal remodeling, and intracellular vesicle trafficking. Drosophila blood cells comprise undifferentiated hemocyte progenitors that exist during the early embryonic stages, and at least three differentiated blood cell types that function in larval and adult stages (Evans & Banerjee, 2003; Hartenstein, 2006; Lanot, Zachary, Holder, & Meister, 2001; Lemaitre et al., 1996): plasmatocytes, crystal cells, and lamellocytes. Plasmatocytes display phagocytic activity and represent the functional equivalents of mammalian monocytes/macrophages.
The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm
2011, Developmental BiologyCitation Excerpt :Aside from this late embryonic/postembryonic “definitive” phase of blood development, there exists, just as in vertebrates, an early, “primitive” phase of blood formation that takes place in the mesoderm of the head of the early embryo (Tepass et al., 1994; Holz et al., 2003; Evans et al., 2003; de Velasco et al., 2006). Molecular factors specifying cells of the blood-vascular and nephrocyte lineages, as well as the signaling mechanisms controlling the expression of these factors, are highly conserved among all animals (reviewed in Zaffran et al., 2002; Evans and Banerjee, 2003; Hartenstein and Mandal, 2006; Hartenstein, 2006; Crozatier and Meister, 2007; Martinez-Agosto et al., 2007). Hemangioblasts of the vertebrate lateral plate and Drosophila cardiogenic mesoderm are induced from naive mesoderm by several signaling pathways that include Bone morphogenetic protein (BMP)/Decapentaplegic (Dpp) and fibroblast growth factor (FGF)/Heartless (Htl).
In vivo detection of lamellocytes in Drosophila melanogaster
2009, Immunology Letters