Ureteric bud

The ureteric bud develops into the ureter, and the swelling at its end becomes the renal pelvis. The repeated branching of the ureteric bud results in the formation of the major and minor calyces (the large ducts that empty into the renal pelvis) and the system of collecting tubules. The two major calyces form from the first branching of the ureteric bud, around the end of the 6th week. 

After induction, two events occur condensation of the mesenchyme around the ureteric bud, and transformation of the mesenchyme into epithelium. In order for condensation into a comma-shaped mass to occur, there has to be induction of a critical mass of cells, not all of which appear to be in contact with the ureteric bud. There appears to be some short-range signalling in the mesenchyme involving the secreted glycoprotein WNT-4. Mice lacking WNT-4 fail to form pretubular aggregates (as do PAX-2 knockouts). There also appears to be migration of induced cells away from direct contact with the ureteric bud, often several cell diameters distant. This may permit uninduced cells to contact the ureteric bud. 

Defects in the ENS are significant in view of the association of RET with Hirshsprung s disease. The ENS derives from neural crest cells which express Ret when in the developing gut and both Gdnf and Gfr-al are expressed in the gut mesenchyme. Lack of kidneys in mutant mouse embryos is due to the failure of the ureteric bud (which expresses Ret) to develop from the Wolffian duct and expand into the metanephric blastema (which expresses Gdnf). This would normally initiate the formation of the metanephric (adult) kidney, but in the absence of ligand or receptor the blastemal cells eventually die. 

Thus, the metanephric mesenchyme contains multipotent progenitors or embryonic renal stem cells with the ability to generate, in concert with the ureteric bud, many cell types in the mature kidney. While the ultimate goal is the identification of a single nephrogenic stem cell that... 

Fig. 15.1 (a) A simplified scheme of an embryonic renal progenitor unit consisting of metanephric mesenchymal stem cells and ureteric buds, which cross-talk via growth factors (GFs) and their receptors, molecules of the extracellular matrix (ECM) and specific integrins, proto-oncogenes and specific ligands and give rise to the differentiated cell types of the adult kidney (see text). 

Recent advances in the understanding of the molecular biology of rodent renal development have enabled the separate culture of the components of the developing rat kidney, namely the ureteric bud and the metanephric mesenchyme. Functionally recombining subcultures of each of... 

Sakurai H, Bush KT, Nigam SK. identification of pleiotrophin as a mesenchymal factor involved in ureteric bud branching morphogenesis. Development 2001 128 3283-3293. 

Qiao J, Bush KT, Steer DL, et al. Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech. Dev. 2001 109 123-135. 

Xia, Y., Nivet, E., Sancho-Martinez, I., Gallegos, T., Suzuki, K., Okamura, D. Wu, M.-Z., Dubova, I., Esteban, C.R., Montserrat, N., Campistol, J.M., and Izpisua Belmonte, J.C. (2013) Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat. Cell Biol. 15, 1507-1515. 

Srinivas S, Goldberg MR, Watanabe T, D Agati V, al-Awqati Q, Costantini F. 1999. Expression of green fluorescent protein in the ureteric bud of transgenic mice a new tool for the analysis of ureteric bud morphogenesis. Dev Genet 24(3 ) 241-251. 

Recently increased attention has been paid to the ureteric bud theory of Mackie and Stephens (Ichikawa et al. 2002 Mackie and Stephens 1975 Pope et al. 1999). Some authors have ascribed the acronym CAKUT (congenital anomalies of the... 

Nephron formation begins in about the 8th week in small foci of metanephric blastema adjacent to the ampulla of the ureteric bud. Approximately 1 million nephrons at different stages of maturation are present in the kidney at birth. Although maturation of the nephrons proceeds after birth, no new nephrons are formed. Growth in the kidney continues until adult life, mainly as a result of elongation of the proximal convoluted tubules and loops of Henle and an increase in the size of the interstitium. 

The definitive kidney, the metanephros, has a dual mesoderm origin. The glomeruli and tubules arise from metanephric blastema, the excretory segments from the ureteric bud. 

Renal ectopy is the term for a kidney lying outside the renal fossa. As stated in Chapter 2 (Sect. 2.1.1), the kidney migrates cephalad early in gestation to arrive at its normal position. Abnormality of the ureteral bud or metanephric blastema, genetic abnormalities, teratogenic causes, or anomalous vasculature, acting as a barrier to ascent, are reasons for failure of the kidney to complete its ascent (Malek et al. 1971). The incidence of renal ectopy in postmortem studies varies from 1 in 500 (Campbell 1930) to 1 in 1,290 (Thompson and Pace 1937). There is a slight predilection for the left side, and 10% of cases are bilateral (Fig. 4.1). 

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