Reactive oxygen species-dependent Toll/ NF-kB activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism

International audienceHematopoietic stem/progenitor cells in the adult mammalian bone marrow ensure blood cell renewal. Their cellular microenvironment, called 'niche', regulates hematopoiesis both under homeostatic and immune stress conditions. In the Drosophila hematopoietic organ, the lymph gland, the posterior signaling center (PSC) acts as a niche to regulate the hematopoietic response to immune stress such as wasp parasitism. This response relies on the differentiation of lamellocytes, a cryptic cell type, dedicated to pathogen encapsulation and killing. Here, we establish that Toll/NF-kB pathway activation in the PSC in response to wasp parasitism non-cell autonomously induces the lymph gland immune response. Our data further establish a regulatory network where co-activation of Toll/NF-kB and EGFR signaling by ROS levels in the PSC/niche controls lymph gland hematopoiesis under parasitism. Whether a similar regulatory network operates in mammals to control emergency hematopoiesis is an open question

Temporally Regulated Traffic of HuR and Its Associated ARE-Containing mRNAs from the Chromatoid Body to Polysomes during Mouse Spermatogenesis

International audienceBACKGROUND: In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation. CONCLUSIONS/SIGNIFICANCE: Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation

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

Stimulation of endocytosis and actin dynamics by Oskar polarizes the Drosophila oocyte.

In Drosophila, localized activity of oskar at the posterior pole of the oocyte induces germline and abdomen formation in the embryo. Oskar has two isoforms, a short isoform encoding the patterning determinant and a long isoform of unknown function. Here, we show by immuno-electron microscopy that the two Oskar isoforms have different subcellular localizations in the oocyte: Short Oskar mainly localizes to polar granules, and Long Oskar is specifically associated with endocytic membranes along the posterior cortex. Our cell biological and genetic analyses reveal that Oskar stimulates endocytosis, and that its two isoforms are required to regulate this process. Furthermore, we describe long F-actin projections at the oocyte posterior pole that are induced by and intermingled with Oskar protein. We propose that Oskar maintains its localization at the posterior pole through dual functions in regulating endocytosis and F-actin dynamics

Drosophila hematopoiesis under normal conditions and in response to immune stress

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Two Independent Functions of Collier/Early B Cell Factor in the Control of Drosophila Blood Cell Homeostasis.

Blood cell production in the Drosophila hematopoietic organ, the lymph gland, is controlled by intrinsic factors and extrinsic signals. Initial analysis of Collier/Early B Cell Factor function in the lymph gland revealed the role of the Posterior Signaling Center (PSC) in mounting a dedicated cellular immune response to wasp parasitism. Further, premature blood cell differentiation when PSC specification or signaling was impaired, led to assigning the PSC a role equivalent to the vertebrate hematopoietic niche. We report here that Collier is expressed in a core population of lymph gland progenitors and cell autonomously maintains this population. The PSC contributes to lymph gland homeostasis by regulating blood cell differentiation, rather than by maintaining core progenitors. In addition to PSC signaling, switching off Collier expression in progenitors is required for efficient immune response to parasitism. Our data show that two independent sites of Collier/Early B Cell Factor expression, hematopoietic progenitors and the PSC, achieve control of hematopoiesis

Identification of Bipotential Blood Cell/Nephrocyte Progenitors in Drosophila: Another Route for Generating Blood Progenitors

International audienceThe Drosophila lymph gland is the larval hematopoietic organ and is aligned along the anterior part of the cardiovascular system, composed of cardiac cells, that form the cardiac tube and its associated pericardial cells or nephrocytes. By the end of embryogenesis the lymph gland is composed of a single pair of lobes. Two additional pairs of posterior lobes develop during larval development to contribute to the mature lymph gland. In this study we describe the ontogeny of lymph gland posterior lobes during larval development and identify the genetic basis of the process. By lineage tracing we show here that each posterior lobe originates from three embryonic pericardial cells, thus establishing a bivalent blood cell/nephrocyte potential for a subset of embryonic pericardial cells. The posterior lobes of L3 larvae posterior lobes are composed of heterogeneous blood progenitors and their diversity is progressively built during larval development. We further establish that in larvae, homeotic genes and the transcription factor Klf15 regulate the choice between blood cell and nephrocyte fates. Our data underline the sequential production of blood cell progenitors during larval development

Identification of Bipotential Blood Cell/Nephrocyte Progenitors in Drosophila: Another Route for Generating Blood Progenitors

International audienceThe Drosophila lymph gland is the larval hematopoietic organ and is aligned along the anterior part of the cardiovascular system, composed of cardiac cells, that form the cardiac tube and its associated pericardial cells or nephrocytes. By the end of embryogenesis the lymph gland is composed of a single pair of lobes. Two additional pairs of posterior lobes develop during larval development to contribute to the mature lymph gland. In this study we describe the ontogeny of lymph gland posterior lobes during larval development and identify the genetic basis of the process. By lineage tracing we show here that each posterior lobe originates from three embryonic pericardial cells, thus establishing a bivalent blood cell/nephrocyte potential for a subset of embryonic pericardial cells. The posterior lobes of L3 larvae posterior lobes are composed of heterogeneous blood progenitors and their diversity is progressively built during larval development. We further establish that in larvae, homeotic genes and the transcription factor Klf15 regulate the choice between blood cell and nephrocyte fates. Our data underline the sequential production of blood cell progenitors during larval development