Architectural patterns in branching morphogenesis in the kidney.

Abstract

During kidney development, several discrete steps generate its three-dimensional pattern including specific branch types, regional differential growth of stems, the specific axes of growth and temporal progression of the pattern. The ureteric bud undergoes three different types of branching. In the first, terminal bifid type, a lateral branch arises and immediately bifurcates to form two terminal branches whose tips induce the formation of nephrons. After 15 such divisions (in humans) of this specifically renal type of branching, several nephrons are induced whose connecting tubules fuse and elongate to form the arcades. Finally, the last generations undergo strictly lateral branching to form the cortical system. The stems of these branches elongate in a highly regulated pattern. The molecular basis of these processes is unknown and we briefly review their potential mediators. Differential growth in three different axes of the kidney (cortico-medullary, dorsoventral and rostro-caudal) generate the characteristic shape of the kidney. Rapid advances in molecular genetics highlight the need for development of specific assays for each of these discrete steps, a prerequisite for identification of the involved pathways. The identification of molecules that control branching (the ultimate determinant of the number of nephrons) has acquired new urgency with the recent suggestion that a reduced nephron number predisposes humans to hypertension and to progression of renal failure.