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Therefore, a deeper understanding of the key signals required for lineage specifica-
tion in vivo is essential for the induction of desired cell types. Presently, the precise
mechanisms underlying kidney development during early embryogenesis are largely
unknown (Dressler 2009 ; Taguchi et al. 2014 ; Taguchi and Nishinakamura 2014 ).
This is in part attributable to the unique developmental processes that were acquired
during evolution of the kidney. Here we review recent advances in the understand-
ing of early kidney specification and its recapitulation by pluripotent stem cells.
These advances have been obtained largely by the combination of in vivo biological
and ex vivo directed stem cell differentiation approaches.
9.2 Kidney Function and Structure
The kidney filters blood to produce urine, thereby facilitating excretion of metabolic
waste and extra fluid from the body. Renal arteries branch directly from the aorta,
and the kidneys receive approximately one-fifth of resting cardiac output to promote
filtration efficiency. This filtration function is accomplished by millions of individ-
ual filtration units—nephrons. Each nephron comprises a filtering apparatus—a
renal corpuscle—and a connecting tubule unit, a nephric tubule. The nephric tubule
balances the fluid volume, pH, and ion concentration of urine. The renal corpuscle
contains characteristic arterioles which are covered by epithelial podocytes to form
the glomerulus. Slit diaphragms form between the cellular foot processes of podo-
cytes, serving as a molecular filtration barrier to prevent the leakage of blood pro-
teins and cellular components. Each nephron is connected to the collecting ducts
and urine then drains through the ureter to the bladder. This complex and sophisti-
cated architecture is essential for the function of the kidney.
9.3 Overview of Kidney Organogenesis In Vivo
The kidney is a unique organ that developed during evolution when animals made
the transition from water to land. In mammals, three distinct primordia—proneph-
ros, mesonephros, and metanephros—form in an anterior-to-posterior direction
along the body trunk during embryogenesis (Fig. 9.1). The pronephros is the most
basic form and is found in mature primitive fish. The mesonephros is found in other
fishes and amphibians. Both the pronephros and mesonephros appear transiently
and then regress during mammalian gestation, though the functionality of these
primitive rudiments varies among species (Saxen 1987 ). In mice, a rudimentary
pronephros arises at embryonic day 8.5 (E8.5), and the mesonephros subsequently
appears at E9.5–E10.0 posterior to the forelimb position. The metanephros then
develops at E10.5 at the hind limb level of the body trunk.
A. Taguchi and R. Nishinakamura