155pronephrosmesonephrosmetanephrosFig. 9.1 Schematic of an
E10.5 embryo. The kidney
develops from three
distinct primordia—
pronephros, mesonephros,
and metanephros—in an
anterior-to-posterior
direction
9.3.1 Interdependent Progenitor Interaction Is Required
for Mature Kidney Architecture
The adult kidney is derived from the embryonic metanephros. The metanephros is
anatomically divided into mesenchymal blastema—the metanephric mesenchyme
(MM)—and epithelial blastema, the ureteric bud (UB). The MM contains at least
three types of progenitors: nephron progenitors, stromal progenitors, and vascular
endothelial cells (Fig. 9.2a). Nephron progenitors express the transcription factor
Six2 and give rise to most of the epithelial nephron components, including glomeru-
lar podocytes, proximal tubules, loop of Henle, and distal tubules (Self et al. 2006 ;
Kobayashi et al. 2008 ; Osafune et al. 2006 ). Stromal progenitors express Foxd1 and
contribute to interstitial cells, smooth muscle cells, and mesangial cells (Humphreys
et al. 2010 , Kobayashi et al. 2014 ). Importantly, interactions among these cell popu-
lations enable the maintenance of a progenitor cell population at the periphery of the
embryonic metanephros in a so-called nephrogenic zone and the continuous pro-
duction of epithelialized nephron structures inside the layer (Fig. 9.2b). In the
mouse, this serial generation of nephrons continues up to postnatal day 3, ultimately
yielding tens of thousands of individual nephrons within a kidney.
9.3.2 Signals that Maintain the Ureteric Bud and Nephron
Progenitors
Recent progress in the field of developmental biology has identified several key
signals that are required for the maintenance and differentiation of nephron and
ureteric progenitors (Fig. 9.2a). Glial cell line-derived neurotrophic factor (Gdnf) is
9 Early Kidney Specification and Its Recapitulation by Pluripotent Stem Cells