Renal branching morphogenesis: concepts, questions, and recent advances

The ureteric bud (UB) is an outgrowth of the Wolffian duct, which undergoes a complex process of growth, branching, and remodeling, to eventually give rise to the entire urinary collecting system during kidney development. Understanding the mechanisms that control this process is a fascinating problem in basic developmental biology, and also has considerable medical significance. Over the past decade, there has been significant progress in our understanding of renal branching morphogenesis and its regulation, and this review focuses on several areas in which there have been recent advances. The first section deals with the normal process of UB branching morphogenesis, and methods that have been developed to better observe and describe it. The next section discusses a number of experimental methodologies, both established and novel, that make kidney development in the mouse a powerful and attractive experimental system. The third section discusses some of the cellular processes that are likely to underlie UB branching morphogenesis, as well as recent data on cell lineages within the growing UB. The fourth section summarizes our understanding of the roles of two groups of growth factors that appear to be particularly important for the regulation of UB outgrowth and branching: GDNF and FGFs, which stimulate this process via tyrosine kinase receptors, and members of the TGF beta family, including BMP4 and Activin A, which generally inhibit UB formation and branching.