Adult stem cell regulation in the drosophila gastrointestinal tract

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.

The long-term maintenance of an organism's homeostasis and health relies on the accurate regulation of organ-organ communication. Recently, there has been growing interest in using the Drosophila gastrointestinal tract to elucidate the regulatory programs that underlie the complex interactions between organs. Data obtained in this field have dramatically improved our understanding of how organ-organ communication contributes to the regulation of various aspects of the intestine, including its metabolic and physiological status.

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We provide evidence that the Wg signaling pathway, activation of which peaks at each of the major compartment boundaries of the adult intestine, has essential functions. Wg pathway activation in the intestinal epithelium is required not only to specify cell fate near compartment boundaries during development, but also to control ISC proliferation within compartments during homeostasis. Further, in contrast with the previous focus on Wg pathway activation within ISCs, we demonstrate that the primary mechanism by which Wg signaling regulates ISC proliferation during homeostasis is non-autonomous.

Abstract The gastrointestinal GI tract of metazoans is lined by a series of regionally distinct epithelia. To maintain structure and function of the GI tract, regionally diversified differentiation of somatic stem cell SC lineages is critical. The adult Drosophila midgut provides an accessible model to study SC regulation and specification in a regionally defined manner. Bmp-like Decapentaplegic Dpp signaling determines the identity of GSSCs, and is required for CC regenerationyet the precise control of Dpp signaling activity in this lineage remains to be fully established.

The Inter active Fly Genes involved in tissue and organ development. It should be kept in mind that the most terminal aspects of the embryo are fated to become gut endoderm. The terminal system torsoregulating tailless and huckebein are responsible for this fate determination.

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Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems. Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell ISC self-renewal in Drosophila adult midgut. The employment of gut epithelia as a niche for stem cell self-renewal may provide a mechanism for direct communication between the niche and the environment, allowing niche signal production and stem cell number to be fine-tuned in response to various physiological and pathological stimuli.

The gastrointestinal tract serves as a fast-renewing model for unraveling the multifaceted molecular mechanisms underlying remarkably rapid cell renewal, which is exclusively fueled by a small number of long-lived stem cells and their progeny. Stem cell activity is the best-characterized aspect of mucosal homeostasis in mitotically active tissues, and the dysregulation of regenerative capacity is a hallmark of epithelial immune defects. This dysregulation is frequently associated with pathologies ranging from chronic enteritis to malignancies in humans.

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The goal of the proposed investigation is to establish an experimental model to study stem cell-based control of adult muscle homeostasis in the genetically tractable system, Drosophila melanogaster. Many of the key cellular, molecular and physiological hallmarks of muscle biology are conserved between invertebrates and mammals Augustin and Partridge, Therefore, if successful, our pilot study will pave the way for subsequent identification of conserved genes controlling the process of adult muscle homeostasis in vivo, using the unsurpassed molecular genetic screening methodologies available only in the fruit fly. Adult tissue homeostasis often depends on a single cell type with the capacity to act as a reservoir of renewal potential, replacing old cells that are lost through injury or disease Morrison and Spradling,

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Research focused on the regulation of the adult stem cells that line the gastrointestinal tract of Drosophila suggests new models for the study of Barrett's esophagus. Barrett's esophagus, a risk factor for esophageal cancer, is a condition in which the cells of the lower esophagus transform into stomach-like cells. In most cases this transformation has been thought to occur directly from chronic acid indigestion when stomach contents flow back up into the esophagus.

Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut epithelium renewal. Here, we addressed how both infectious and indigenous bacteria modulate stem cell activity in Drosophila. We show that the increased epithelium renewal observed upon some bacterial infections is a consequence of the oxidative burst, a major defense of the Drosophila gut.


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