19611.1.1 Formation of the Mammalian Kidney
Studies into the development of the mammalian kidney, largely performed in mouse,
have provided much information about the progenitor populations present during
foetal development that give rise to the distinct cell types of the kidney. In mam-
mals, it is the metanephric kidneys which persist after birth, while the pronephroi
and mesonephroi degenerate during foetal development. These metanephric kid-
neys are structurally distinct in that rather than being comprised of a series of simple
tubules draining into the nephric duct, they form via the interaction between an
epithelial side branch of the nephric duct, called the ureteric bud (Fig. 11.2). This
ureteric bud (UB) forms as a swelling of the nephric duct in line with the hindlimbs.
The UB then grows towards a domain of mesoderm, the metanephric mesenchyme
(MM), expressing the growth factor glial-derived neurotrophic factor (GDNF). In
response to GDNF from the MM, the UB upregulates RET and GFRα1, co- receptors
for this ligand (Costantini and Kopan 2010 ). Once the UB reaches the MM, this
ligand-receptor interaction triggers feed-forward signalling in which the UB begins
to dichotomously branch within the MM while the MM is induced to upregulate
GDNF to further support this process (Costantini and Kopan 2010 ). Ret signalling
induces cell proliferation and migration within the tips of the branching ureteric tree
as well as producing Wnt ligands that support the surrounding self-renewal of thePPSPSIM MMNDUBrostralcaudalUECMMMRVUESSBFig. 11.2 Embryology of the kidney. The permanent kidney in mammals, the metanephros, is
mesodermal in origin. The early embryo undergoes gastrulation to form the primitive streak (PS)
which gives rise to the endoderm and mesoderm germ layers. The posterior end of the primitive
streak (PPS) is the region from which the mesoderm of the embryo forms. Along the trunk of the
embryo, the paraxial, intermediate and lateral plate mesoderm arises. The anterior end of the inter-
mediate mesoderm (IM) gives rise to the nephric duct (ND) which extends along the embryo as it
forms. A more posterior region of the IM gives rise to the metanephric mesenchyme (MM). This
population induces the formation of a side branch of the ND. This is the ureteric bud (UB) which
grows towards the MM and begins to branch as a ureteric epithelium (UE). The branching UE will
mature into the collecting ducts of the kidney. MM cells closest to the tips of the branching UE will
form the cap mesenchyme (CM). This has been shown to be the progenitor population for all of the
cells of the nephron. Induction of nephron formation via a mesenchyme to epithelial transition first
forms an epithelial renal vesicle (RV) which patterns and segments to form the S-shaped body
(SSB) from which the nephron elongates and matures. The surrounding MM contributes to the
interstitium/stroma of the kidney, some of which contributes to the perivascular and mesangial
cells. It is thought that at least a portion of the vasculature also arises from the MM
M.H. Little et al.