Stromally Expressed β-Catenin Modulates Wnt9b Signaling in the Ureteric Epithelium

التفاصيل البيبلوغرافية
العنوان: Stromally Expressed β-Catenin Modulates Wnt9b Signaling in the Ureteric Epithelium
المؤلفون: Bruno Svajger, Hadiseh Khalili, Ashkan Javidan, Darren Bridgewater, Janice Lim, Sanjay Sarin, Felix J. Boivin
المصدر: PLoS ONE
PLoS ONE, Vol 10, Iss 3, p e0120347 (2015)
بيانات النشر: Public Library of Science, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Male, medicine.medical_specialty, Cell type, Mesenchyme, Population, lcsh:Medicine, Kidney development, Nephron, Biology, urologic and male genital diseases, Kidney, Gene Knockout Techniques, Mice, Stroma, Internal medicine, medicine, Animals, Progenitor cell, lcsh:Science, education, beta Catenin, education.field_of_study, Multidisciplinary, urogenital system, lcsh:R, Cell biology, Wnt Proteins, medicine.anatomical_structure, Endocrinology, Gene Expression Regulation, lcsh:Q, Female, Stromal Cells, Ureter, Urothelium, Gene Deletion, Research Article, Signal Transduction
الوصف: The mammalian kidney undergoes cell interactions between the epithelium and mesenchyme to form the essential filtration unit of the kidney, termed the nephron. A third cell type, the kidney stroma, is a population of fibroblasts located in the kidney capsule, cortex and medulla and is ideally located to affect kidney formation. We found β-catenin, a transcriptional co-activator, is strongly expressed in distinctive intracellular patterns in the capsular, cortical, and medullary renal stroma. We investigated β-catenin function in the renal stroma using a conditional knockout strategy that genetically deleted β-catenin specifically in the renal stroma cell lineage (β-cats-/-). β-cats-/- mutant mice demonstrate marked kidney abnormalities, and surprisingly we show β-catenin in the renal stroma is essential for regulating the condensing mesenchyme cell population. We show that the population of induced mesenchyme cells is significantly reduced in β-cats-/- mutants and exhibited decreased cell proliferation and a specific loss of Cited 1, while maintaining the expression of other essential nephron progenitor proteins. Wnt9b, the key signal for the induction of nephron progenitors, was markedly reduced in adjacent ureteric epithelial cells in β-cats-/-. Analysis of Wnt9b-dependent genes in the neighboring nephron progenitors was significantly reduced while Wnt9b-independent genes remained unchanged. In contrast mice overexpressing β-catenin exclusively in the renal stroma demonstrated massive increases in the condensing mesenchyme population and Wnt9b was markedly elevated. We propose that β-catenin in the renal stroma modulates a genetic program in ureteric epithelium that is required for the induction of nephron progenitors.
اللغة: English
تدمد: 1932-6203
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efdd5317dd69fcdc3b9f11daeec674e6
http://europepmc.org/articles/PMC4372213
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....efdd5317dd69fcdc3b9f11daeec674e6
قاعدة البيانات: OpenAIRE