Abstract
The kidneys play a critical homeostatic role in the regulation of body fluid composition and excretion of waste products. Here I review our understanding of how the three different vertebrate kidney types (pronephros, mesonephros, and metanephros) arise during mouse development with a more comprehensive focus on the molecular regulation of metanephros formation. A detailed understanding of the genetic hierarchies governing renal development will provide insights into the pathogenesis of kidney disorders, advance efforts to direct pluripotent stem cells into therapeutically useful renal lineages in vitro, and further our understanding of renal regenerative pathways that occur in vivo.
Highlights
The kidneys are bilateral organs that regulate the composition and volume of the body fluids, and eliminate metabolic waste products
Studies demonstrated that reciprocal and inductive signaling between the ureteric bud (UB) and the metanephric mesenchyme are essential for initiating and maintaining the cycles of UB branching and nephron induction that underlie the formation of the metanephros (Grobstein, 1955; Grobstein, 1956)
The foot processes are anchored to a specialized basal lamina, called the glomerular basement membrane (GBM), which serves to separate the podocytes from the underlying endothelium
Summary
The kidneys are bilateral organs that regulate the composition and volume of the body fluids, and eliminate metabolic waste products. Mammalian renal development differs from that of most other organs in that it proceeds through a series of three successive phases, each marked by the formation of a more complex pair of kidneys These kidneys, which are called the pronephros, mesonephros, and metanephros, develop in a cranial (anterior)-to-caudal (posterior) progression from stripes of mesodermal cells, called the intermediate mesoderm, that extend from the heart region to the tailbud of the embryo (see Figure 2). The mammalian metanephros comprises an inner medullary region (containing collecting ducts and long loops of Henle—the nephron segment involved in urine concentration), an outer medullary region (containing short Loops of Henle and collecting ducts), and a cortical region (containing all other domains of the nephron; Figure 1) This gross structure is important for the functionality of the metanephric kidney as it establishes an osmotic gradient between the cortex and medulla that drives the extraction of water from the urine (Fenton and Knepper, 2007). Studies demonstrated that reciprocal and inductive signaling between the UB and the metanephric mesenchyme are essential for initiating and maintaining the cycles of UB branching and nephron induction that underlie the formation of the metanephros (Grobstein, 1955; Grobstein, 1956)
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