The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning

Abstract

The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney.

Figure 1. A schematic diagram of mammalian kidney development

Metanephric kidney development commences when a ureteric bud (UB) outgrowth from the nephric duct (ND) invades the metanephric mesenchyme (MM) of the posterior nephric cord (NC). The ureteric bud undergoes repeated rounds of branching morphogenesis to form the collecting duct system, while a subset of the nephron progenitors in the cap mesenchyme (CM) is induced by the ureteric bud epithelium to undergo nephrogenesis. Nephron progenitors epithelialize to form the renal vesicle (RV), which further develops into the S-shaped body (SSB) before fully develop into a nephron. The kidneys are divided into the cortex (C) and the medulla (M), each enriched with different nephron and collecting duct segments. RI, renal interstitium.

Figure 2. A schematic diagram of the spatial distribution of mature renal epithelial structures along the cortico-medullary axis

There are two types of nephrons, the cortical nephrons, of which the loops of Henle reach only into the outer medulla, and the juxtamedullary nephrons, of which the loops of Henle reach into the inner medulla. RC, renal corpuscle; PCT, proximal convoluted tubules; PST, proximal straight tubules; DTL, thin descending limb (of the loop of Henle); ATL, thin ascending limb (of the loop of Henle); TAL, thick ascending limb (of the loop of Henle); DCT, distal convoluted tubule; CNT, connecting tubule; CD, collecting duct.