Abstract: Current kidney organoids model development and diseases of the nephron but not the con-tiguous epithelial network of the kidney's collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or gen-erated de novo from human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of adult kidney's collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Applying a gene editing strategy to remove RET activity, we demonstrate genetically modified UB organoids can model congenital anomalies of kidney and urinary tract (CAKUT).