Morphogenesis of the Metanephric Kidney

Abstract

The metanephric (permanent) kidney of the mouse is an exceptionally well-studied example of organ development. Its morphogenesis begins on the meeting of two tissues, the epithelial ureteric bud and the metanephrogenic mesenchyme; a series of signalling events between these tissues and their successors organizes the organ as it grows and matures. Many of the signals have been identified at the molecular level. They include GDNF, neurturin, persephin, HGF, BMP-2, BMP-7, FGF-10, activin, and TGFβ (all of which control development of the ureteric bud); TGFα, TIMP-2, BMP-4, and BMP7 (all of which control development of the mesenchyme); LIF, FGF-2, TGFβ, Wnt-4, sFrp, Notch, and Jagged (all of which control nephron development); and VEGF (which controls vascularization). Many of these signals are arranged in feedback loops, so that cells entering one developmental pathway signal back to ensure that other cells are more likely to enter alternative pathways, and thus keep the relative proportions and positions of different renal tissues in balance.