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secreted by nephron progenitor cells to signal via the tyrosine kinase receptor ret
proto-oncogene (Ret) on the ureteric epithelia to enable dichotomous branching
morphogenesis (Vega et al. 1996 ; Shakya et al. 2005 ). This signal network is posi-
tively coordinated by UB tip-derived Wnt11  in an autoregulatory feedback loop
manner (Majumdar 2003 ; Kispert et al. 1996 ). Contrastingly, Fgf9 from the ureteric
epithelium concomitant with the Fgf20-expressing nephron progenitor itself main-
tains the immature nephron progenitors on the surface of the ureteric tips (Barak
et  al. 2012 ). Bmp7 and canonical Wnt signaling have also been identified as the
maintenance signals for nephron progenitors (Karner et  al. 2011 ; Muthukrishnan
et al. 2015 ). Additional to these interactions between the UB and capping mesen-
chyme, stromal cells are also important for UB branching and nephron

Stromal cell

Ureteric bud

Capping mesenchyme

(nephron progenitor)

Fgf20

Fgf9 Wnt11

Wnt9b

Gdnf

Endothelial cell

a

Comma-shaped body

Endothelial cell

S-shaped body

Ureteric bud

Capping mesenchyme

b Renal vesicle

nephron

Collecting duct

Ureteric stalk

Nephrogenic

zone

Fig. 9.2 Schematic of a developing metanephros. (a) The metanephric rudiment at E11.5 contains
several progenitor types: stromal cells, capping mesenchyme, endothelial cells, and the ureteric
bud. (b) Schematic of E15.5 metanephros. The capping mesenchyme (nephron progenitor) differ-
entiates into an epithelial nephron by way of the renal vesicle, comma-shaped body, and S-shaped
body. The peripheral kidney cortex, or “nephrogenic zone,” contains an immature cell population,
including nephron progenitors, ureteric bud tips, and cortical stromal progenitors (pink-colored
layer)

A. Taguchi and R. Nishinakamura