First Author | Deacon E | Year | 2023 |
Journal | Dev Dyn | Volume | 252 |
Issue | 9 | Pages | 1224-1239 |
PubMed ID | 37227110 | Mgi Jnum | J:340939 |
Mgi Id | MGI:7531594 | Doi | 10.1002/dvdy.603 |
Citation | Deacon E, et al. (2023) beta-Catenin in the kidney stroma modulates pathways and genes to regulate kidney development. Dev Dyn 252(9):1224-1239 |
abstractText | BACKGROUND: Kidney 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. RESULTS: We 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. CONCLUSIONS: These 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. |