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β‐Catenin in the renal stroma regulates apoptosis via Bcl2l1 during kidney development (344.4)
Author(s) -
Boivin Felix,
Bridgewater Darren
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.344.4
Subject(s) - stromal cell , mesenchyme , stroma , kidney development , catenin , microbiology and biotechnology , biology , cancer research , apoptosis , population , kidney , embryonic stem cell , wnt signaling pathway , medicine , endocrinology , immunology , signal transduction , mesenchymal stem cell , gene , immunohistochemistry , genetics , environmental health
Kidney development is dependent upon reciprocal inductive interactions between epithelium, mesenchyme, and stroma cells. β‐catenin is essential for the formation of mesenchyme derived nephrons and epithelial derived collecting duct system. β‐catenin protein is expressed in medullary, cortical, and capsular stroma in embryonic and mature kidneys. However, its role in the renal stroma is not well understood. We generated mice with ß‐catenin deficiency exclusively in the renal stroma (termed ß‐catLOF‐S). Kidneys from ß‐catLOF‐S demonstrated a paucity of renal capsule and a significant reduction in the stromal cell population (4.55 +/‐ 0.19 stromal cells/mm2 WT vs 2.52 +/‐ 0.26 in ß‐catLOF‐S). Analysis of apoptosis in ß‐catLOF‐S revealed a significant increase in apoptotic stromal cells by E13.5 (0.54 +/‐ 0.03 WT apoptotic cells/mm2 vs 1.19 +/‐ 0.14 in ß‐catLOF‐S). We investigated β‐catenin targets that regulate apoptosis and observed significant reductions in Bcl2l1 mRNA and protein in ß‐catLOF‐S kidneys. We demonstrate β‐catenin forms a novel molecular complex with transcriptional co‐activators TBX5, YAP1, and YES1, and binds to the TBX5 consensus site within the Bcl2l1 promoter. These results suggest β‐catenin controls stromal cell survival via regulation of Bcl2l1 by forming a novel transcriptional complex during kidney development. Grant Funding Source : Supported by NSERC (Natural Sciences and Engineering Research Council of Canada) and KFOC (The Kidne