10 - The Metanephros

Abstract

This chapter focuses on the development of the mammalian metanephric kidney, the third and final member of a triad of renal tissues whose development within the intermediate mesoderm begins after the formation of the anetrioposterior axis. The chapter also provides the details of the kidney development and the underlying molecular mechanisms. The chapter provides a sufficient background about the kidney formation and growth. Metanephros development in all higher vertebrates starts with the demarcation of the metanephric blastema in the caudal part of each intermediate mesoderm. This blastema is a domain of a few thousand cells, known as “metanephric mesenchyme” (MM) that expresses two key transcription factors—WT1 and Pax-2—and is 1–200 μm from the medial mesonephric duct that is coursing toward the cloaca and future bladder. Demarcation takes place at about E10 in the mouse and E30 in the human. Cells of this blastema give rise to nephron, stromal, neuronal, endothelial, and smooth muscle cells as well as the juxtaglomerular complex and capillaries, although it is unknown that how many independent lineages are represented in the blastema. Each metanephric blastema soon secretes glial-derived neural growth factor, (GDNF), and this signal interacts with the adjacent mesonephric duct that expresses c-ret, the GDNF receptor, and its coreceptor GFR-1a. As a result of this interaction, the bud is induced to sprout and form the ureteric bud that extends toward and then invades its nearby blastema. As the ureteric bud grows and bifurcates, the growing tips of the collecting ducts reciprocally induce the metanephric mesenchyme by secreting signals that have a range of inductive effects on the MM.