scholarly journals The ureteric bud epithelium: Morphogenesis and roles in metanephric kidney patterning

2015 ◽  
Vol 82 (3) ◽  
pp. 151-166 ◽  
Author(s):  
Vidya K. Nagalakshmi ◽  
Jing Yu
Keyword(s):  
Ureteric Bud ◽  
Metanephric Kidney

Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3627-3637 ◽  
Author(s):  
A. Kispert ◽  
S. Vainio ◽  
L. Shen ◽  
D.H. Rowitch ◽  
A.P. McMahon
Keyword(s):  
Collecting Duct ◽  
Expression Patterns ◽  
Branching Morphogenesis ◽  
Proteoglycan Synthesis ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Metanephric Kidney ◽  
Specific Factors ◽  
Collecting Duct Epithelium ◽  
Metanephric Blastema

Development of the metanephric kidney requires the concerted interaction of two tissues, the epithelium of the ureteric duct and the metanephric mesenchyme. Signals from the ureter induce the metanephric mesenchyme to condense and proliferate around the ureter tip, reciprocal signals from the mesenchyme induce the ureter tip to grow and to branch. Wnt genes encode secreted glycoproteins, which are candidate mediators of these signaling events. We have identified three Wnt genes with specific, non-overlapping expression patterns in the metanephric kidney, Wnt-4, Wnt-7b and Wnt-11. Wnt-4 is expressed in the condensing mesenchyme and the comma- and S-shaped bodies. Wnt-7b is expressed in the collecting duct epithelium from 13.5 days post coitum onward. Wnt-1l is first expressed in the nephric duct adjacent to the metanephric blastema prior to the outgrowth of the ureteric bud. Wnt-l1 expression in Danforth's short-tail mice suggests that signaling from the mesenchyme may regulate Wnt-ll activation. During metanephric development, Wnt-11 expression is confined to the tips of the branching ureter. Maintenance of this expression is independent of Wnt-4 signaling and mature mesenchymal elements in the kidney. Moreover, Wnt-ll expression is maintained in recombinants between ureter and lung mesenchyme suggesting that branching morphogenesis and maintenance of Wnt-ll expression are independent of metanephric mesenchyme-specific factors. Interference with proteoglycan synthesis leads to loss of Wnt-ll expression in the ureter tip. We suggest that Wnt-11 acts as an autocrine factor within the ureter epithelium and that its expression is regulated at least in part by proteoglycans.

scholarly journals Genetic Dissection of Cadherin Function during Nephrogenesis

2002 ◽  
Vol 22 (5) ◽  
pp. 1474-1487 ◽  
Author(s):  
Ulf Dahl ◽  
Anders Sjödin ◽  
Lionel Larue ◽  
Glenn L. Radice ◽  
Stefan Cajander ◽  
...  
Keyword(s):  
Kidney Development ◽  
Morphological Changes ◽  
Genetic Dissection ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Metanephric Kidney ◽  
The Individual ◽  
Deficient Mice

ABSTRACT The distinct expression of R-cadherin in the induced aggregating metanephric mesenchyme suggests that it may regulate the mesenchymal-epithelial transition during kidney development. To address whether R-cadherin is required for kidney ontogeny, R-cadherin-deficient mice were generated. These mice appeared to be healthy and were fertile, demonstrating that R-cadherin is not essential for embryogenesis. The only kidney phenotype of adult mutant animals was the appearance of dilated proximal tubules, which was associated with an accumulation of large intracellular vacuoles. Morphological analysis of nephrogenesis in R-cadherin −/− mice in vivo and in vitro revealed defects in the development of both ureteric bud-derived cells and metanephric mesenchyme-derived cells. First, the morphology and organization of the proximal parts of the ureteric bud epithelium were altered. Interestingly, these morphological changes correlated with an increased rate of apoptosis and were further supported by perturbed branching and patterning of the ureteric bud epithelium during in vitro differentiation. Second, during in vitro studies of mesenchymal-epithelial conversion, significantly fewer epithelial structures developed from R-cadherin −/− kidneys than from wild-type kidneys. These data suggest that R-cadherin is functionally involved in the differentiation of both mesenchymal and epithelial components during metanephric kidney development. Finally, to investigate whether the redundant expression of other classic cadherins expressed in the kidney could explain the rather mild kidney defects in R-cadherin-deficient mice, we intercrossed R-cadherin −/− mice with cadherin-6−/− , P-cadherin −/−, and N-cadherin +/− mice. Surprisingly, however, in none of the compound knockout strains was kidney development affected to a greater extent than within the individual cadherin knockout strains.

scholarly journals Protein Kinase X Activates Ureteric Bud Branching Morphogenesis in Developing Mouse Metanephric Kidney

2005 ◽  
Vol 16 (12) ◽  
pp. 3543-3552 ◽  
Author(s):  
Xiaohong Li ◽  
Deborah P. Hyink ◽  
Katalin Polgar ◽  
G. Luca Gusella ◽  
Patricia D. Wilson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Branching Morphogenesis ◽  
Ureteric Bud ◽  
Metanephric Kidney

TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis

Development ◽  
2001 ◽  
Vol 128 (7) ◽  
pp. 1045-1057 ◽  
Author(s):  
S.Y. Plisov ◽  
K. Yoshino ◽  
L.F. Dove ◽  
K.G. Higinbotham ◽  
J.S. Rubin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Tubule Formation ◽  
Wnt Ligands ◽  
Metanephric Kidney ◽  
Beta 2

The metanephric kidney develops from interactions between the epithelial ureteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron. We have found that leukemia inhibitory factor (LIF) and transforming growth factor beta 2 (TGF beta 2) are secreted by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF alone or TGF beta 2 with fibroblast growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day period, while (in combination) all three caused abundant tubule formation in 72 hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abrogated these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF and TGF beta 2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism.

scholarly journals Morphogenesis of the Metanephric Kidney

2002 ◽  
Vol 2 ◽  
pp. 1937-1950 ◽  
Author(s):  
Jamie A. Davies
Keyword(s):  
Molecular Level ◽  
Feedback Loops ◽  
Organ Development ◽  
Ureteric Bud ◽  
Developmental Pathway ◽  
Alternative Pathways ◽  
Metanephric Kidney ◽  
Nephron Development

The metanephric (permanent) kidney of the mouse is an exceptionally well-studied example of organ development. Its morphogenesis begins on the meeting of two tissues, the epithelial ureteric bud and the metanephrogenic mesenchyme; a series of signalling events between these tissues and their successors organizes the organ as it grows and matures. Many of the signals have been identified at the molecular level. They include GDNF, neurturin, persephin, HGF, BMP-2, BMP-7, FGF-10, activin, and TGFβ (all of which control development of the ureteric bud); TGFα, TIMP-2, BMP-4, and BMP7 (all of which control development of the mesenchyme); LIF, FGF-2, TGFβ, Wnt-4, sFrp, Notch, and Jagged (all of which control nephron development); and VEGF (which controls vascularization). Many of these signals are arranged in feedback loops, so that cells entering one developmental pathway signal back to ensure that other cells are more likely to enter alternative pathways, and thus keep the relative proportions and positions of different renal tissues in balance.

scholarly journals Hoxa11andHoxd11regulate branching morphogenesis of the ureteric bud in the developing kidney

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2153-2161 ◽  
Author(s):  
Larry T. Patterson ◽  
Martina Pembaur ◽  
S. Steven Potter
Keyword(s):  
Gene Expression ◽  
Kidney Development ◽  
Growth Failure ◽  
Immunohistochemical Analysis ◽  
Branching Morphogenesis ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Metanephric Kidney ◽  
Normal Gene ◽  
Ureteric Buds

Hoxa11 and Hoxd11 are functionally redundant during kidney development. Mice with homozygous null mutation of either gene have normal kidneys, but double mutants have rudimentary, or in extreme cases, absent kidneys. We have examined the mechanism for renal growth failure in this mouse model and find defects in ureteric bud branching morphogenesis. The ureteric buds are either unbranched or have an atypical pattern characterized by lack of terminal branches in the midventral renal cortex. The mutant embryos show that Hoxa11 and Hoxd11 control development of a dorsoventral renal axis. By immunohistochemical analysis, Hoxa11 expression is restricted to the early metanephric mesenchyme, which induces ureteric bud formation and branching. It is not found in the ureteric bud. This suggests that the branching defect had been caused by failure of mesenchyme to epithelium signaling. In situ hybridizations with Wnt7b, a marker of the metanephric kidney, show that the branching defect was not simply the result of homeotic transformation of metanephros to mesonephros. Absent Bf2 and Gdnf expression in the midventral mesenchyme, findings that could by themselves account for branching defects, shows that Hoxa11 and Hoxd11 are necessary for normal gene expression in the ventral mesenchyme. Attenuation of normal gene expression along with the absence of a detectable proliferative or apoptotic change in the mutants show that one function of Hoxa11 and Hoxd11 in the developing renal mesenchyme is to regulate differentiation necessary for mesenchymal-epithelial reciprocal inductive interactions.

scholarly journals Dynamic regulation of sphingosine-1-phosphate homeostasis during development of mouse metanephric kidney

2009 ◽  
Vol 296 (3) ◽  
pp. F634-F641 ◽  
Author(s):  
R. Jason Kirby ◽  
Ying Jin ◽  
Jian Fu ◽  
Jimena Cubillos ◽  
Debi Swertfeger ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Kidney Development ◽  
Sphingosine Kinase ◽  
Branching Morphogenesis ◽  
Lipid Mediator ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Dynamic Regulation ◽  
Sphingosine 1 Phosphate ◽  
Metanephric Kidney

Branching morphogenesis of the metanephric kidney is critically dependent on the delicate orchestration of diverse cellular processes including proliferation, apoptosis, migration, and differentiation. Sphingosine-1-phosphate (S1P) is a potent lipid mediator influencing many of these cellular events. We report increased expression and activity of both sphingosine kinases and S1P phosphatases during development of the mouse metanephric kidney from induction at embryonic day 11.5 to maturity. Sphingosine kinase activity exceeded S1P phosphatase activity in embryonic kidneys, resulting in a net accumulation of S1P, while kinase and phosphatase activities were similar in adult tissue, resulting in reduced S1P content. Sphingosine kinase expression was greater in the metanephric mesenchyme than in the ureteric bud, while the S1P phosphatase SPP2 was expressed at greater levels in the ureteric bud. Treatment of cultured embryonic kidneys with sphingosine kinase inhibitors resulted in a dose-dependent reduction of ureteric bud tip numbers and increased apoptosis. Exogenous S1P rescued kidneys from apoptosis induced by kinase inhibitors. Ureteric bud tip number was unaffected by exogenous S1P in kidneys treated with N, N-dimethylsphingosine, although tip number increased in those treated with d,l- threo-dihydrosphingosine. S1P1 and S1P2 were the predominant S1P receptors expressed in the embryonic kidney. S1P1 expression increased during renal development while expression of S1P2 decreased, and both receptors were expressed predominantly in the metanephric mesenchyme. These results demonstrate dynamic regulation of S1P homeostasis during renal morphogenesis and suggest that differential expression of S1P metabolic enzymes and receptors provides a novel mechanism contributing to the regulation of kidney development.

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