Geometric effects position renal vesicles during kidney development

During kidney development, reciprocal signaling between the epithelium and the mesenchyme coordinates nephrogenesis with branching morphogenesis of the collecting ducts. The mechanism that positions the renal vesicles, and thus the nephrons, relative to the branching ureteric buds has remained elusive. By combining computational modeling and experiments, we show that geometric effects concentrate the key regulator, WNT9b, at the junctions between parent and daughter branches where renal vesicles emerge, even when uniformly expressed in the ureteric epithelium. This curvature effect might be a general paradigm to create non-uniform signaling in development. [Display omitted] •Geometric effects concentrate morphogen at kidney branch junctions•Curvature effect as a paradigm for spatially modulating development•Experimental evidence supports WNT9b concentration at branch junctions•Example of reciprocal epithelial-mesenchymal signal coordination Mederacke et al. show that geometric effects concentrate WNT9b, the most upstream inducer of nephrogenesis, at the branch corners of the ureteric tree. Thereby, nephrogenesis in the metanephric mesenchyme and branching morphogenesis of the ureteric tree are coordinated such that a single nephron connects at each branchpoint.