Host-diet-microbiota interplay in intestinal nutrition and health.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier.

The Sterol Transporter Npc2c Controls Intestinal Stem Cell Mitosis and Host-Microbiome Interactions in .

Cholesterol is necessary for all cells to function. The intracellular cholesterol transporters Npc1 and Npc2 control sterol trafficking and their malfunction leads to Neimann-Pick Type C disease, a rare disorder affecting the nervous system and the intestine. Unlike humans that encode single Npc1 and Npc2 transporters, flies encompass two Npc1 (Npc1a-1b) and eight Npc2 (Npc2a-2h) members, and most of the family genes remain unexplored.

Biotin controls intestinal stem cell mitosis and host-microbiome interactions.

Diet is a key regulator of metabolism and interacts with the intestinal microbiome. Here, we study the role of the Drosophila intestinal stem cell (ISC)-specific biotin transporter Smvt in midgut homeostasis, infection-induced regeneration, and tumorigenesis. We show that Smvt-transported biotin in ISCs is necessary for ISC mitosis.

How Gut Microbes Nurture Intestinal Stem Cells: A Perspective.

Host-microbiota interactions are key modulators of host physiology and behavior. Accumulating evidence suggests that the complex interplay between microbiota, diet and the intestine controls host health. Great emphasis has been given on how gut microbes have evolved to harvest energy from the diet to control energy balance, host metabolism and fitness.

Histone acetyltransferase NAA40 modulates acetyl-CoA levels and lipid synthesis.

Background: Epigenetic regulation relies on the activity of enzymes that use sentinel metabolites as cofactors to modify DNA or histone proteins. Thus, fluctuations in cellular metabolite levels have been reported to affect chromatin modifications. However, whether epigenetic modifiers also affect the levels of these metabolites and thereby impinge on downstream metabolic pathways remains largely unknown.

Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila.

The Drosophila trachea, as the functional equivalent of mammalian blood vessels, senses hypoxia and oxygenates the body. Here, we show that the adult intestinal tracheae are dynamic and respond to enteric infection, oxidative agents and tumours with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated regeneration and is sufficient to drive ISC proliferation in undamaged intestines.

Evidence of two types of balance between stem cell mitosis and enterocyte nucleus growth in the midgut.

Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult midgut of different genetic backgrounds.

Unpredictable Effects of the Genetic Background of Transgenic Lines in Physiological Quantitative Traits.

Physiology, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of the Genetics Reference Panel to assess the phenotypic variation of six physiological and fitness traits, namely, female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia.

Tissue communication in regenerative inflammatory signaling: lessons from the fly gut.

The intestine, as a barrier epithelium, serves in the first line of defense against invading pathogens and damaging agents that enter the body via food ingestion. Maintenance of intestinal homeostasis is therefore key to organismal health. To maintain homeostasis, intestinal stem cells (ISCs) continuously replace lost or damaged intestinal epithelial cells in organisms ranging from Drosophila to humans.

The homeobox transcription factor cut coordinates patterning and growth during Drosophila airway remodeling.

A fundamental question in developmental biology is how tissue growth and patterning are coordinately regulated to generate complex organs with characteristic shapes and sizes. We showed that in the developing primordium that produces the Drosophila adult trachea, the homeobox transcription factor Cut regulates both growth and patterning, and its effects depend on its abundance. Quantification of the abundance of Cut in the developing airway progenitors during late larval stage 3 revealed that the cells of the developing trachea had different amounts of Cut, with the most proliferative region having an intermediate amount of Cut and the region lacking Cut exhibiting differentiation.

Signaling mechanisms controlling cell fate and embryonic patterning.

During development, signaling pathways specify cell fates by activating transcriptional programs in response to extracellular signals. Extensive studies in the past 30 years have revealed that surprisingly few pathways exist to regulate developmental programs and that dysregulation of these can lead to human diseases, including cancer. Although these pathways use distinct signaling components and signaling strategies, a number of common themes have emerged regarding their organization and regulation in time and space.

Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells.

Although pathogenic bacteria are suspected contributors to colorectal cancer progression, cancer-promoting bacteria and their mode of action remain largely unknown. Here we report that sustained infection with the human intestinal colonizer Pseudomonas aeruginosa synergizes with the Ras1V12 oncogene to induce basal invasion and dissemination of hindgut cells to distant sites. Cross-talk between infection and dissemination requires sustained activation by the bacteria of the Imd-dTab2-dTak1 innate immune pathway, which converges with Ras1V12 signalling on JNK pathway activation, culminating in extracellular matrix degradation.

Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis.

Adult structures in holometabolous insects such as Drosophila are generated by groups of imaginal cells dedicated to the formation of different organs. Imaginal cells are specified in the embryo and remain quiescent until the larval stages, when they proliferate and differentiate to form organs. The Drosophila tracheal system is extensively remodeled during metamorphosis by a small number of airway progenitors.

Synergy between bacterial infection and genetic predisposition in intestinal dysplasia.

Accumulating evidence suggests that hyperproliferating intestinal stem cells (SCs) and progenitors drive cancer initiation, maintenance, and metastasis. In addition, chronic inflammation and infection have been increasingly recognized for their roles in cancer. Nevertheless, the mechanisms by which bacterial infections can initiate SC-mediated tumorigenesis remain elusive.

Homeostasis in infected epithelia: stem cells take the lead.

To maintain tissue homeostasis and avoid disease, epithelial cells damaged by pathogens need to be readily replenished, and this is mainly achieved by the activation of stem cells. In this Short Review, we discuss recent developments in the exciting field of host epithelia-pathogen interaction in Drosophila as well as in mammals.

Mesoscopic fluorescence tomography for in-vivo imaging of developing Drosophila.

Visualizing developing organ formation as well as progession and treatment of disease often heavily relies on the ability to optically interrogate molecular and functional changes in intact living organisms. Most existing optical imaging methods are inadequate for imaging at dimensions that lie between the penetration limits of modern optical microscopy (0.5-1mm) and the diffusion-imposed limits of optical macroscopy (>1cm) [1].

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes.

A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues.

In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography.

We report a technique for fluorescence tomography that operates beyond the penetration limits of tissue-sectioning fluorescence microscopy. The method uses multi-projection illumination and photon transport description in opaque tissues. We demonstrate whole-body three-dimensional visualization of the morphogenesis of GFP-expressing salivary glands and wing imaginal discs in living Drosophila melanogaster pupae in vivo and over time.

Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis.

Notch is the receptor in a signalling pathway that operates in a diverse spectrum of developmental processes. Its ligands (e.g.

The interplay between DSL proteins and ubiquitin ligases in Notch signaling.

Lateral inhibition is a pattern refining process that generates single neural precursors from a field of equipotent cells and is mediated via Notch signaling. Of the two Notch ligands Delta and Serrate, only the former was thought to participate in this process. We now show that macrochaete lateral inhibition involves both Delta and Serrate.