beta-catenin in the kidney stroma modulates pathways and genes that regulate kidney development

BackgroundKidney development is regulated by cellular interactions between the ureteric epithelium, mesenchyme, and stroma. Previous studies demonstrate essential roles for stromal beta-catenin in kidney development. However, how stromal beta-catenin regulates kidney development is not known. We hypothesize that stromal beta-catenin modulates pathways and genes that facilitate communications with neighboring cell populations to regulate kidney development. ResultsWe isolated purified stromal cells with wild type, deficient, and overexpressed beta-catenin by fluorescence-activated cell sorting and conducted RNA Sequencing. A Gene Ontology network analysis demonstrated that stromal beta-catenin modulates key kidney developmental processes, including branching morphogenesis, nephrogenesis and vascular formation. Specific stromal beta-catenin candidate target genes that may mediate these effects included secreted, cell-surface and transcriptional factors that regulate branching morphogenesis and nephrogenesis (Wnts, Bmp, Fgfr, Tcf/Lef) and secreted vascular guidance cues (Angpt1, VEGF, Sema3a). We validated established beta-catenin targets including Lef1 and novel candidate beta-catenin targets including Sema3e which have unknown roles in kidney development. ConclusionsThese studies advance our understanding of gene and biological pathway dysregulation in the context of stromal beta-catenin misexpression during kidney development. Our findings suggest that during normal kidney development, stromal beta-catenin may regulate secreted and cell-surface proteins to communicate with adjacent cell populations.