Hematopoietic progenitors and hemocyte lineages in the Drosophila lymph gland

AbstractThe Drosophila lymph gland (LG) is a model system for studying hematopoiesis and blood cell homeostasis. Here, we investigated the patterns of division and differentiation of pro-hemocytes in normal developmental conditions and response to wasp parasitism, by combining lineage analyses and molecular markers for each of the three hemocyte types. Our results show that the embryonic LG contains primordial hematopoietic cells which actively divide to give rise to a pool of pro-hemocytes. We found no evidence for the existence of bona fide stem cells and rather suggest that Drosophila pro-hemocytes are regulated as a group of cells, rather than individual stem cells. The fate-restriction of plasmatocyte and crystal cell progenitors occurs between the end of embryogenesis and the end of the first larval instar, while Notch activity is required for the differentiation of crystal cells in third instar larvae only. Upon parasitism, lamellocyte differentiation prevents crystal cell differentiation and lowers plasmatocyte production. We also found that a new population of intermediate progenitors appears at the onset of hemocyte differentiation and accounts for the increasing number of differentiated hemocytes in the third larval instar. These findings provide a new framework to identify parameters of developmental plasticity of the Drosophila lymph gland and hemocyte homeostasis in physiological conditions and in response to immunological cues

The metazoan history of the COE transcription factors. Selection of a variant HLH motif by mandatory inclusion of a duplicated exon in vertebrates

<p>Abstract</p> <p>Background</p> <p>The increasing number of available genomic sequences makes it now possible to study the evolutionary history of specific genes or gene families. Transcription factors (TFs) involved in regulation of gene-specific expression are key players in the evolution of metazoan development. The low complexity COE (Collier/Olfactory-1/Early B-Cell Factor) family of transcription factors constitutes a well-suited paradigm for studying evolution of TF structure and function, including the specific question of protein modularity. Here, we compare the structure of <it>coe </it>genes within the metazoan kingdom and report on the mechanism behind a vertebrate-specific exon duplication.</p> <p>Results</p> <p>COE proteins display a modular organisation, with three highly conserved domains : a COE-specific DNA-binding domain (DBD), an Immunoglobulin/Plexin/transcription (IPT) domain and an atypical Helix-Loop-Helix (HLH) motif. Comparison of the splice structure of <it>coe </it>genes between cnidariae and bilateriae shows that the ancestral COE DBD was built from 7 separate exons, with no evidence for exon shuffling with other metazoan gene families. It also confirms the presence of an ancestral H1LH2 motif present in all COE proteins which partly overlaps the repeated H2d-H2a motif first identified in rodent EBF. Electrophoretic Mobility Shift Assays show that formation of COE dimers is mediated by this ancestral motif. The H2d-H2a α-helical repetition appears to be a vertebrate characteristic that originated from a tandem exon duplication having taken place prior to the splitting between gnathostomes and cyclostomes. We put-forward a two-step model for the inclusion of this exon in the vertebrate transcripts.</p> <p>Conclusion</p> <p>Three main features in the history of the <it>coe </it>gene family can be inferred from these analyses: (i) each conserved domain of the ancestral <it>coe </it>gene was built from multiple exons and the same scattered structure has been maintained throughout metazoan evolution. (ii) There exists a single <it>coe </it>gene copy per metazoan genome except in vertebrates. The H2a-H2d duplication that is specific to vertebrate proteins provides an example of a novel vertebrate characteristic, which may have been fixed early in the gnathostome lineage. (iii) This duplication provides an interesting example of counter-selection of alternative splicing.</p

A Short Receptor Downregulates JAK/STAT Signalling to Control the Drosophila Cellular Immune Response

Regulation of JAK/STAT signalling by a short, nonsignalling receptor in Drosophila modulates response to specific immune challenges such as parasitoid infestations

Caractérisation moléculaire et fonctionnelle de la niche hématopoïétique de Drosophila melanogaster

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias

Vertebrate haematopoietic stem cells (HSCs) give rise to a hierarchically organised set of progenitors for erythroid, myeloid, lymphoid and megakaryocyte lineages, and are responsible for lifelong maintenance of the blood system. Dysregulation of the haematopoietic differentiation programme is at the origin of numerous pathologies, including leukaemias. With the discoveries that many transcriptional regulators and signalling pathways controlling blood cell development are conserved between humans and Drosophila melanogaster, the fruit fly has become a good model for investigating the mechanisms underlying the generation of blood cell lineages and blood cell homeostasis. In this review article, we discuss how genetic and molecular studies of Drosophila haematopoiesis can contribute to our understanding of the haematopoietic niche, as well as of the origin and/or progression of haematopoietic malignancies in humans

Patterns in evolution: veins of the Drosophila wing.

The development of the Drosophila wing is a classical model for studying the genetic control of tissue size, shape and patterning. A detailed picture of how positional information is interpreted by cells in the imaginal disc and translated into the adult wing vein pattern has recently emerged. It highlights the central role of dose-dependent activation of distinct cell transcription programs in response to the Hedgehog (Hh) and Decapentaplegic (Dpp) morphogens, as well as an early role of Notch signalling, in connecting the positioning of vein primordia and vein differentiation proper. The biochemical basis of the cross-talk that operates between these different signalling pathways is less well understood. New strategies made possible by the genome sequencing of several insect models should provide an important complement to the knowledge obtained from >60 years of genetic studies

The hematopoietic niche: a Drosophila model, at last.

The niche provides a specialised microenvironment necessary for maintenance of stem cells in a non differentiated state. While the hematopoietic stem cell (HSC) niche in vertebrates was the first to be recognized, Drosophila niches supporting germline stem cells were characterised first. Recent evidence for the existence of a niche maintaining hematopoietic precursors in Drosophila opens the way to study in vivo the niche/hematopoietic precursors interactions. The availability of a large collection of cell markers, mutants and sophisticated genetic tools makes Drosophila an attractive model for investigating the cellular and molecular mechanisms that are involved in these interactions

Vein-positioning in the Drosophila wing in response to Hh; new roles of Notch signaling.

The Drosophila wing is a classical model for studying the generation of developmental patterns. Previous studies have suggested that vein primordia form at boundaries between discrete sectors of gene expression along the antero-posterior (A/P) axis in the larval wing imaginal disc. Observation that the vein marker rhomboid (rho) is expressed at the centre of wider vein-competent domains led to propose that narrow vein primordia form first, and produce secondary short-range signals activating provein genes in neighbouring cells (see Curr. Opin. Genet. Dev. 10 (2000) 393). Here, we examined how the central L3 and L4 veins are positioned relative to the limits of expression of Collier (Col), a dose-dependent Hedgehog (Hh) target activated in the wing A/P organiser. We found that rho expression is first activated in broad domains adjacent to Col-expressing cells and secondarily restricted to the centre of these domains. This restriction which depends upon Notch (N) signaling sets the L3 and L4 vein primordia off the boundaries of Col expression. N activity is also required to fix the anterior limit of Col expression by locally antagonising Hh activation, thus precisely positioning the L3 vein primordium relative to the A/P compartment boundary. Experiments using Nts mutants further indicated that these two activities of N could be temporally uncoupled. Together, these observations highlight new roles of N in topologically linking the position of veins to prepattern gene expression

La niche hématopoïétique de la drosophile

Le maintien et la fonction des cellules souches qui assurent le renouvellement des tissus sont dépendants du microenvironnement de ces cellules, désigné par le terme « niche ». Chez les mammifères, plusieurs voies de signalisation ont été impliquées dans les communications entre les cellules souches hématopoïétiques et leur niche. Nos connaissances de ces communications restent cependant fragmentaires. La découverte chez la drosophile d’une niche hématopoïétique, le posterior signaling center (PSC), a ouvert de nouvelles possibilités d’études génétiques. Le nombre des cellules du PSC est déterminant pour l’homéostasie entre progéniteurs hématopoïétiques et cellules différenciées. Le décryptage d’une cascade de signalisation contrôlant cette taille a établi de nouveaux parallèles entre la drosophile et les mammifères, et ouvert de nouvelles perspectives d’étude chez l’homme

Expression patterns of the coe/ebf transcription factor genes during chicken and mouse limb development.

The COE (Collier/Olf/EBF) family of transcription factors comprises a single member in Drosophila and four members in human and mice. We have examined by in situ hybridization the expression patterns of each ebf/coe gene during limb development in mouse and chicken embryos. Expression of mouse ebf1, 2 and 3 is detected in mesenchymal cells from stages E10.5-11, expression of ebf2 being restricted to the presumptive zeugopod. Cross sections of mouse and chicken limb buds at several stages reveal that ebfs are specifically expressed in the connective tissues surrounding chondrogenic condensations and forming tendons. They thus represent useful new markers for studying vertebrate limb development, particularly formation of ligaments