Biology subjects

Kondo, S.

Publications and source records attributed to Kondo, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Mod(mdg4) variants repress telomeric retrotransposonHeT-A by blocking subtelomeric enhancers

Telomeres in Drosophila are composed of sequential non-LTR retrotransposons: HeT-A, TART, and TAHRE. Although they are repressed by the piRNA pathway in the germline, how these retrotransposons are regulated in somatic cells is poorly understood. Here, we show that specific splice variants of Mod(mdg4) repress HeT-A by blocking subtelomeric enhancers in ovarian somatic cells. We found that the Mod(mdg4)-N variant represses HeT-A expression most efficiently among the variants. Mod(mdg4)-N mutant flies show elevated HeT-A expression and female sterility. Mod(mdg4)-N-binding subtelomeric sequences exhibit enhancer-blocking activity, and recruitment of RNA polymerase II (Pol II) on subtelomeres by Mod(mdg4)-N is essential for this enhancer-blocking. Moreover, Mod(mdg4)-N functions to form chromatin boundaries of higher-order chromatin conformation but this mechanism is independent of its Pol II recruitment activity at telomeres/subtelomeres. This study provides a link between enhancer-blocking and telomere regulation, and two different molecular mechanisms exhibited by an insulator protein to orchestrate precise gene expression.

molecular biology↗

bioRxiv2021

CCN2 activates ERK-signaling via integrin αv and enhances the interaction of ERK and DUSP6 in lymphatic endothelial cells

Cellular communication network factor 2 (CCN2, also known as CTGF), is a modular and matricellular protein and a well-known angiogenic factor in physiological and pathological angiogenesis. However, its roles in lymphangiogenesis and intracellular signaling in lymphatic endothelial cells (LECs) remain unclear. Here, we investigated CCN2 signaling in LECs and its effects on lymphangiogenesis. In primary cultured LECs, gene expressions of lymphatic endothelial markers lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1), Podoplanin and prospero homeobox 1 (Prox1) and lymphangiogenic factors vascular endothelial cell growth factor c (Vegfc), vascular endothelial cell growth factor d (Vegfd) and fms-related tyrosine kinase 4 (Flt4, also known as Vegfr3) were upregulated by CCN2. Subsequently, we found that CCN2 induced phospho-ERK and that was decreased by suppression of integrin v. CCN2 slightly decreased the growth of LECs due to enhancement of the interaction of ERK and dual specific protein phosphatase 6 (DUSP6), and knockdown of DUSP6 increased CCN2-induced phospho-ERK levels. In in vivo Matrigel plug assays, the number of Podoplanin-positive vessels was increased by exogenous CCN2, and phospho-ERK-positive LEC and DUSP6-positive LEC were detected in CCN2 plugs. These results suggest that CCN2-related lymphangiogenesis is regulated by DUSP6, which enables negative modulation of ERK-signaling.

cell biology↗

bioRxiv2021

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

The enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins in mammals. Although glucagon-like and insulin-like hormones have been found across animal phyla, incretin-like EEC-derived hormones have not yet been characterised in invertebrates. Here, we show that the midgut-derived hormone, Neuropeptide F (NPF), acts as the sugar-responsive, incretin-like hormone in the fruit fly, Drosophila melanogaster. Secreted NPF is received by NPF receptor in the corpora cardiaca and in insulin-producing cells. NPF-NPFR signalling resulted in the suppression of the glucagon-like hormone production and the enhancement of the insulin-like peptide secretion, eventually promoting lipid anabolism. Similar to the loss of incretin function in mammals, loss of midgut NPF led to significant metabolic dysfunction, accompanied by lipodystrophy, hyperphagia, and hypoglycaemia. These results suggest that enteroendocrine hormones regulate sugar-dependent metabolism through glucagon-like and insulin-like hormones not only in mammals but also in insects.

physiology↗

bioRxiv2021

Drosophila antimicrobial peptides and lysozymes regulate gut microbiota composition and abundance

The gut microbiota affects the physiology and metabolism of animals and its alteration can lead to diseases such as gut dysplasia or metabolic disorders. Several reports have shown that the immune system plays an important role in shaping both bacterial community composition and abundance in Drosophila, and that immune deficit, especially during aging, negatively affects microbiota richness and diversity. However, there has been little study at the effector level to demonstrate how immune pathways regulate the microbiota. A key set of Drosophila immune effectors are the antimicrobial peptides (AMPs), which confer defense upon systemic infection. AMPs and lysozymes, a group of digestive enzymes with antimicrobial properties, are expressed in the gut and are good candidates for microbiota regulation. Here, we take advantage of the model organism Drosophila melanogaster to investigate the role of AMPs and lysozymes in regulation of gut microbiota structure and diversity. Using flies lacking AMPs and newly generated lysozyme mutants, we colonized gnotobiotic flies with a defined set of commensal bacteria and analyzed changes in microbiota composition and abundance in vertical transmission and aging contexts through 16S rRNA gene amplicon sequencing. Our study shows that AMPs and, to a lesser extent, lysozymes are necessary to regulate the total and relative abundance of bacteria in the gut microbiota. We also decouple the direct function of AMPs from the IMD signaling pathway that regulates AMPs but also many other processes, more narrowly defining the role of these effectors in the microbial dysbiosis observed in IMD-deficient flies upon aging. ImportanceThis study advances current knowledge in the field of host-microbe interactions by demonstrating that the two families of immune effectors, antimicrobial peptides and lysozymes, actively regulate the gut microbiota composition and abundance. Consequences of the loss of these antimicrobial peptides and lysozymes are exacerbated during aging, and their loss contributes to increased microbiota abundance and shifted composition in old flies. This work shows that immune effectors, typically associated with resistance to pathogenic infections, also help shape the beneficial gut community, consistent with the idea that host-symbiont interactions use the same language typically associated with pathogenesis.

microbiology↗

bioRxiv2021

A population of neurons that produce hugin and express the diuretic hormone 44 receptor gene projects to the corpora allata in Drosophila melanogaster

The corpora allata (CA) are essential endocrine organs that biosynthesize and secrete the sesquiterpenoid hormone, namely juvenile hormone (JH), to regulate a wide variety of developmental and physiological events in insects. Previous studies had demonstrated that the CA are directly innervated with neurons in many insect species, implying the innervations to be important for regulating JH biosynthesis in response to internal physiology and external environments. While this is also true for the model organism, Drosophila melanogaster, which neurotransmitters are produced in the CA-projecting neurons are yet to be clarified. In this study on D. melanogaster, we aimed to demonstrate that a subset of neurons producing the neuropeptide hugin, the invertebrate counterpart of the vertebrate neuromedin U, directly projects to the adult CA. A synaptic vesicle marker in the hugin neurons was observed at their axon termini located on the CA, which were immunolabeled with a newly-generated antibody to the JH biosynthesis enzyme JH acid O-methyltransferase (JHAMT). We also found the CA-projecting hugin neurons to likely express a gene encoding the specific receptor for diuretic hormone 44 (Dh44). Moreover, our data suggested that the CA-projecting hugin neurons have synaptic connections with the upstream neurons producing Dh44. To the best of our knowledge, this is the first study to identify a specific neurotransmitter of the CA-projecting neurons in D. melanogaster, and to anatomically characterize a neuronal pathway of the CA-projecting neurons and their upstream neurons.

zoology↗

bioRxiv2021

Evolutionary trajectories of three independent neo-sex chromosomes in Drosophila

Dosage compensation (DC) on the X chromosome is a mechanism to counteract the deleterious effects by gene loss from the Y chromosome. However, DC cannot work efficiently if the X chromosome also degenerates. This indeed occurs in the neo-sex chromosomes in Drosophila miranda, where neo-X as well as neo-Y chromosomes are under accelerated pseudogenization. To examine the generality of this pattern, we investigated the evolution of two additional neo-sex chromosomes that independently emerged in D. albomicans and D. americana and compared their evolutionary processes with that in D. miranda. Comparative genomic and transcriptomic analyses revealed that the pseudogenization rate on neo-X is also accelerated in the two species (though lesser extent in D. americana). We also found that neo-X-linked genes whose neo-Y homologs are pseudogenized tend to be upregulated more stringently than those whose neo-Y homologs remain functional. Moreover, the genes under strong functional constraints and highly expressed in the testis tended to remain functional on neo-X and neo-Y, respectively. Focusing on the D. miranda and D. albomicans neo-sex chromosomes that independently emerged from the same autosome, we further found that the same genes tend to have been pseudogenized in parallel on neo-Y. Those genes include Idgf6 and JhI-26 whose functions seem to be unnecessary or could be even harmful for males. These results indicate that neo-sex chromosomes in Drosophila share a common evolutionary trajectory after their emergence, which may be applicable to other sex chromosomes in a variety of organisms to avoid being an evolutionary dead-end.

evolutionary biology↗

bioRxiv2021

Proapoptotic RHG genes and mitochondria play a key non-apoptotic role in remodelling the Drosophila sensory system

Caspases are best known for their role in programmed cell death but have also been found to be important in several non-apoptotic phenomena such as cell fate specification, cell migration and terminal differentiation. The dynamics of such sub-lethal caspase events and the molecular mechanisms regulating them are still largely unknown. As more tools for visualizing and manipulating caspase activation in vivo become available, greater insights into this biology are being made. Using a new and sensitive in vivo effector caspase probe, called SR4VH, we demonstrate that effector caspases are activated in pruning sensory neurons earlier than previously thought and that the level of caspase activation in these neurons is consistently lower than in neurons undergoing cell death. We reveal that Grim and Reaper, two of the four pro-apoptotic RHG proteins, are required for sensory neuron pruning and that disrupting the dynamics of the mitochondrial network prevents effector caspase activation in both pruning and dying sensory neurons. Overall, our findings demonstrate that a sublethal deployment of the apoptotic machinery is critical for remodelling dendrites and also reveal a direct link between mitochondria and sensory neuron cell death in vivo.

developmental biology↗

bioRxiv2020

Crumbs and the Apical Spectrin Cytoskeleton Regulate R8 Cell Fate in the Drosophila eye

The Hippo pathway is an important regulator of organ growth and cell fate. In the R8 photoreceptor cells of the Drosophila melanogaster eye, the Hippo pathway controls the fate choice between one of two subtypes that express either the blue light-sensitive Rhodopsin 5 (Hippo inactive) or the green light-sensitive Rhodopsin 6 (Hippo active). The degree to which the mechanism of Hippo signal transduction and the proteins that mediate it are conserved in organ growth and R8 cell fate choice is currently unclear. Here, we identify Crumbs and the apical spectrin cytoskeleton as regulators of R8 cell fate. By contrast, other proteins that influence Hippo-dependent organ growth, such as the basolateral spectrin cytoskeleton and Ajuba, are dispensable for the R8 cell fate choice. Surprisingly, Crumbs promotes the Rhodopsin 5 cell fate, which is driven by Yorkie, rather than the Rhodopsin 6 cell fate, which is driven by Warts and the Hippo pathway, which contrasts with its impact on Hippo activity in organ growth. Furthermore, neither the apical spectrin cytoskeleton nor Crumbs regulate the Hippo pathway through mechanisms that have been reported to operate in growing organs. Together, these results show that only a subset of Hippo pathway proteins regulate the R8 binary cell fate decision and that aspects of Hippo pathway signalling appear to differ between growing organs and post-mitotic R8 cells.

genetics↗

bioRxiv2020

Effects of underlying gene-regulation network structure on prediction accuracy in high-dimensional regression

MotivationThe least absolute shrinkage and selection operator (lasso) and principal component regression (PCR) are popular methods of estimating traits from high-dimensional omics data, such as transcriptomes. The prediction accuracy of these estimation methods is highly dependent on the covariance structure, which is characterized by gene regulation networks. However, the manner in which the structure of a gene regulation network together with the sample size affects prediction accuracy has not yet been sufficiently investigated. In this study, Monte Carlo simulations are conducted to investigate the prediction accuracy for several network structures under various sample sizes. ResultsWhen the gene regulation network was random graph, the simulation indicated that models with high estimation accuracy could be achieved with small sample sizes. However, a real gene regulation network is likely to exhibit a scale-free structure. In such cases, the simulation indicated that a relatively large number of observations is required to accurately predict traits from a transcriptome. Availability and implementationSource code at https://github.com/keihirose/simrnet Contacthirose@imi.kyushu-u.ac.jp

bioinformatics↗

bioRxiv2020

Critical role of the periplasm in copper homeostasis in Gram-negative bacteria

Copper is essential for life, but is toxic in excess; that is, cells must keep an optimal internal copper concentration. Under aerobic conditions, less toxic Cu(II) taken up by bacterial cells is reduced to more toxic Cu(I) in the cytoplasm. Copper homeostasis is achieved in the cytoplasm and the periplasm as a unique feature of Gram-negative bacteria. The copper efflux pumps, CopA and CusCBA export Cu(I) from the cytoplasm or the periplasm to outside of the cells in Escherichia coli. In addition, the periplasmic proteins, such as a multi-copper oxidase CueO, play a role in the periplasmic detoxification. While the efflux pumps are highly conserved in Gram-negative bacteria, the periplasmic proteins are diversified, indicating that copper homeostasis in the periplasm could contribute to adaptation to various living environments. However, the role of the periplasm and periplasmic proteins in regard to whole-cell copper homeostasis remains unknown. In this study, we addressed the role of the periplasm and periplasmic proteins in copper homeostasis to adapt to various ecological niches. We have used a systems approach, alternating rounds of experiments and models, to further elucidate the dynamics of copper efflux system. We measured the response to copper of the main specific copper export systems in the wild type E. coli strain, and a series of deletion mutant strains. We interpreted these data using a detailed mathematical model and Bayesian model fitting routines, and verified copper homeostasis. Compared with the simulation and the growth in response to copper, we found that the growth was associated with copper abundance in the periplasm. In particular, CueO unique to Gram-negative bacteria contributes both to protection against Cu(I) toxicity and to incorporating copper into the periplasmic components/proteins, resulting in maximizing the growth. These results suggest that Gram-negative bacteria have evolved to utilize the periplasm as a sensor and store for copper, in order to enable Gram-negative bacteria to adapt to a wide range of environmental copper concentrations.

systems biology↗

bioRxiv2020

Genetical control of 2D pattern and depth of the primordial furrow that codes 3D shape of the rhinoceros beetle horn

The head horn of the Asian rhinoceros beetle develops as extensively folded primordia before unfurling into its final 3D shape at the pupal molt. The information of the final 3D structure of the beetle horn is encoded in the folding pattern of the developing primordia. However, the developmental mechanism underlying epithelial folding of the primordia is unknown. In this study, we addressed this gap in our understanding of the developmental patterning of the 3D horn shape of beetles by focusing on the formation of surficial furrows that become the bifurcated 3D shape of the horn. By gene knockdown screening via RNAi, we found that knockdown of the gene Notch disturbed overall horn primordia furrow depth without affecting 2D furrow pattern. In contrast, knockdown of CyclinE altered 2D horn primordia furrow pattern without affecting furrow depth. From these results, depth and 2D pattern of primordial surficial furrow are likely to be regulated independently during the development and both of change can alter the final 3D shape. Author SummaryIn insects, some large structure is made under the old exoskeleton before the molting. Long horn of rhino-beetle is one of extreme cases. The beetle horn is compactly packed as furrowed primordia under the larval exoskeleton. At molting, the primordia is extended to form its final 3D horn shape as blowing up furrows like a balloon. This transformation from primordia to final horn does not required any living cell activities. Thus, characteristics of furrows of primordia actually determine the final 3D shape. However, molecular mechanisms and genetic basis of furrow formation is not well understood not only in beetle horn but also in any other insects. In this study, by using beetle horn as a model, we addressed what kind of genetic factors are contributed to primordial furrow formation. By gene knockdown screening, we found that knockdown of the gene Notch disturbed primordial furrow depth without affecting 2D furrow pattern. In contrast, knockdown of CyclinE altered 2D furrow pattern without affecting furrow depth. In both case, final horn shapes were disturbed. From these results, we concluded that both of the depth and 2D pattern of primordial furrow can contribute final shape, but their development is controlled independently.

developmental biology↗

bioRxiv2020

Neuronal octopamine signaling regulates mating-induced germline stem cell proliferation in female Drosophila melanogaster

Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to external cues remains poorly understood. Here we report that efferent octopaminergic neurons projecting to the ovary are essential for germline stem cell (GSC) proliferation in response to mating in female Drosophila. The neuronal activity of the octopaminergic neurons is required for mating-induced GSC proliferation as they relay the mating signal from Sex peptide receptor-positive cholinergic neurons. Octopamine and its receptor Oamb are also required for mating-induced GSC proliferation via intracellular Ca2+ signaling. Moreover, we identified Matrix metalloproteinase-2 as a downstream component of the octopamine-Ca2+ signaling to induce GSC proliferation. Our study provides a mechanism describing how neuronal system couples stem cell behavior to external cues through stem cell niche signaling.

developmental biology↗

bioRxiv2020

Continual inactivation of stem cell functional identity genes stabilizes progenitor commitment

Expansion of the pool of stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, mechanistic investigation of the competency of stem cells to generate intermediate progenitors remains impossible. Fly larval brain neuroblasts provide excellent in vivo models for investigating the regulation of stem cell functionality during neurogenesis. Type II neuroblasts undergo indirect neurogenesis by dividing asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as the master regulator that maintains type II neuroblast functional identity, including the competency to generate INPs. Successive inactivation during INP commitment inhibits tll activation by Notch, preventing INPs from reacquiring neuroblast functionality. We propose that the continual inactivation of neural stem cell functional identity genes by histone deacetylation allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.

developmental biology↗

bioRxiv2020

Transcriptome analysis reveals evolutionary co-option of neural development and signaling genes for the wing pigmentation pattern of the polka-dotted fruit fly.

How evolutionary novelties have arisen is one of the central questions in evolutionary biology. Pre-existing gene regulatory networks or signaling pathways have been shown to be co-opted for building novel traits in several organisms. However, the structure of entire gene regulatory networks and evolutionary events of gene co-option for emergence of a novel trait are poorly understood. In this study, we used a novel wing pigmentation pattern of the polka-dotted fruit fly, and identified the complete set of genes for pigmentation pattern formation by de novo genome sequencing and transcriptome analyses. In pigmentation areas of wings, 151 genes were positively or negatively regulated by wingless, a master regulator of wing pigmentation. Genes for neural development, Wnt signaling, Dpp signaling, Zinc finger transcription factors, and effectors (such as enzymes) for melanin pigmentation were included among these 151 genes. None of the known regulatory genes that regulate pigmentation pattern formation in other fruit fly species were included. Our results suggest that the novel pigmentation pattern of the polka-dotted fruit fly emerged through multi-step co-options of multiple gene regulatory networks, signaling pathways, and effector genes, rather than recruitment of one large gene circuit.

developmental biology↗

bioRxiv2019

Neuropeptide F receptor acts in the Drosophila prothoracic gland to regulate growth and developmental timing

As juvenile animals grow, their behaviour, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behaviour and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signalling functions in controlling many aspects of behaviour, physiology and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behaviour, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behaviour with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behaviour from insects to mammals, also regulates development in Drosophila. Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titres. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signalling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signalling plays a key role in regulating animal development and may thus play a global role in integrating feeding behaviour and development in Drosophila.

developmental biology↗

bioRxiv2019

Large-scale transgenic Drosophila resource collections for loss- and gain-of-function studies

The Transgenic RNAi Project (TRiP), a Drosophila functional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute a genome-scale collection of RNAi fly stocks. To date, the TRiP has generated >15,000 RNAi fly stocks. As this covers most Drosophila genes, we have largely transitioned to development of new resources based on CRISPR technology. Here, we present an update on our libraries of publicly available RNAi and CRISPR fly stocks, and focus on the TRiP-CRISPR overexpression (TRiP-OE) and TRiP-CRISPR knockout (TRiP-KO) collections. TRiP-OE stocks express sgRNAs targeting upstream of a gene transcription start site. Gene activation is triggered by co-expression of catalytically dead Cas9 (dCas9) fused to an activator domain, either VP64-p65-Rta (VPR) or Synergistic Activation Mediator (SAM). TRiP-KO stocks express one or two sgRNAs targeting the coding sequence of a gene or genes, allowing for generation of indels in both germline and somatic tissue. To date, we have generated more than 5,000 CRISPR-OE or -KO stocks for the community. These resources provide versatile, transformative tools for gene activation, gene repression, and genome engineering.

genetics↗

bioRxiv2019

Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi.

The Hippo pathway is an evolutionary conserved signalling network that regulates organ size, cell fate control and tumorigenesis. In the context of organ size control, the pathway incorporates a large variety of cellular cues such as cell polarity and adhesion into an integrated transcriptional response. The central Hippo signalling effector is the transcriptional co-activator Yorkie, which controls gene expression in partnership with different transcription factors, most notably Scalloped. When it is not activated by Yorkie, Scalloped can act as a repressor of transcription, at least in part due to its interaction with the corepressor protein Tgi. The mechanism by which Tgi represses transcription is incompletely understood and therefore we sought to identify proteins that potentially operate together with it. Using an affinity purification and mass-spectrometry approach we identified Pits and CtBP as Tgi-interacting proteins, both of which have been linked to transcriptional repression. Both Pits and CtBP were required for Tgi to suppress the growth of the D. melanogaster eye and CtBP loss suppressed the undergrowth of yorkie mutant eye tissue. Furthermore, as reported previously for Tgi, overexpression of Pits suppressed transcription of Hippo pathway target genes. These findings suggest that Tgi might operate together with Pits and CtBP to repress transcription of genes that normally promote tissue growth. The human orthologues of Tgi, CtBP and Pits (VGLL4, CTBP2 and IRF2BP2) physically and functionally interact to control transcription, implying that the mechanism by which these proteins control transcriptional repression is conserved throughout evolution.

developmental biology↗

bioRxiv2019

Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.\n\nAuthor summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.\n\nInterestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

immunology↗