Modeling Renal Disease “On the Fly”

Millet-Boureima, Cassandra; Marroquin, Jessica Porras; Gamberi, Chiara

doi:10.1155/2018/5697436

Cited by 25 publications

(33 citation statements)

References 153 publications

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“…Understanding the genetic pathways involved is crucial, as defects in any of these aforementioned processes can lead to malformations and lethality (Jung et al, 2005;Denholm, 2013;Ainsworth et al, 2000). These events can be readily studied in Drosophila melanogaster Malpighian tubules (MTs), a powerful model system for investigating mechanisms of cell differentiation, proliferation and development, as well as a model of kidney disease (Millet-Boureima et al, 2018;Dow and Romero, 2010).…”

Section: Introductionmentioning

confidence: 99%

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

et al. 2019

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The GATA family of transcription factors is implicated in numerous developmental and physiological processes in metazoans. In Drosophila melanogaster, five different GATA factor genes (pannier, serpent, grain, GATAd and GATAe) have been reported as essential in the development and identity of multiple tissues, including the midgut, heart and brain. Here, we present a novel role for GATAe in the function and homeostasis of the Drosophila renal (Malpighian) tubule. We demonstrate that reduced levels of GATAe gene expression in tubule principal cells induce uncontrolled cell proliferation, resulting in tumorous growth with associated altered expression of apoptotic and carcinogenic key genes. Furthermore, we uncover the involvement of GATAe in the maintenance of stellate cells and migration of renal and nephritic stem cells into the tubule. Our findings of GATAe as a potential master regulator in the events of growth control and cell survival required for the maintenance of the Drosophila renal tubule could provide new insights into the molecular pathways involved in the formation and maintenance of a functional tissue and kidney disease.

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Section: Introductionmentioning

confidence: 99%

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

et al. 2019

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“…Wg/Wnt1 pathway controls differentiation, proliferation, survival, and cell motility during normal development (Clevers, 2006). Abnormal activation of Wnt signaling is associated with and contributes to oncogenesis (Miller, 2002). Wg/Wnt1 signaling pathway has core components as well as positive and negative regulators (Clevers, 2006).…”

Section: Simpler Gene Familiesmentioning

confidence: 99%

Drug screening in Drosophila; why, when, and when not?

2019

WIREs Developmental Biology

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The best global seller among oncology drugs in 2018 is lenalidomide, an analog of thalidomide. It took 53 years and a circuitous route from the discovery of thalidomide to approval of an analog for use in treatment of cancer. We understand now a lot more about the genetic and molecular basis of diseases than we did in 1953 when thalidomide was discovered. We have also no shortage of chemical libraries with hundreds of thousands of compounds, both synthetic and natural. What we need are better ways to search among these rich resources for compounds with the potential to do what we want them to do. This review summarizes examples from the literature that make Drosophila melanogaster a good model to screen for drugs, and discusses knowledge gaps and technical challenges that make Drosophila models not as widely used as they could or should be. This article is categorized under: Technologies > Analysis of Cell, Tissue, and Animal Phenotypes

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“…Homeostasis is accomplished by modification of primary urine as it passes down more proximal regions of the tubule before emptying into the hindgut via the ureters [26].…”

Section: Introductionmentioning

confidence: 99%

Non-apoptotic function of caspase-3 in morphogenesis of epithelial tubes ofDrosophilarenal system

Ojha

Tapadia

2020

Preprint

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Cells trigger apoptosis to eliminate themselves from the system, when tissue needs to be sculptured or they detect any abnormality within them, thus preventing irreparable damage to the host. Drosophila Malpighian tubules express apoptotic proteins, without succumbing to cell death. Here we present evidence to show apoptosis independent role of executioner caspase, Drice, for precise architecture and function of Malpighian tubules. Drice is required for precise cytoskeleton organization and convergent extension, failing which the morphology, size, cellular number and arrangement gets affected. Acquisition of star shape of stellate cells in adult Malpighian tubules requires Drice. We demonstrate that Drice regulates expression of Rho1GTPase and localization of polarity proteins. Our study shows a probable mechanism by which Drice governs tubulogenesis via Rho1GTPase mediated coordinated organization of actin cytoskeleton and membrane stablisation. Furthermore, defective morphology of tubules leads to abnormal osmoregulation and excretory functions. Collectively our findings suggest a possible non-apoptotic function of caspase-3 in the fine tuning of cell mobility during tubule development and our results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans.

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Modeling Renal Disease “On the Fly”

Cited by 25 publications

References 153 publications

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

Drug screening in Drosophila; why, when, and when not?

Non-apoptotic function of caspase-3 in morphogenesis of epithelial tubes ofDrosophilarenal system

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