Spatial and temporal expression of cell surface molecules during nephrogenesis

1997 ◽  
Vol 272 (1) ◽  
pp. F79-F86 ◽  
Author(s):  
M. R. Goldberg ◽  
J. Barasch ◽  
A. Shifteh ◽  
V. D'Agati ◽  
J. A. Oliver ◽  
...  
Keyword(s):  
Kidney Development ◽  
Cell Interaction ◽  
Mesenchymal Cells ◽  
Cell Contact ◽  
Distinctive Pattern ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Temporal Expression ◽  
Functional Effect ◽  
Surface Molecules

Cell-to-cell interaction is fundamental to the development of the kidney. Ureteric bud cells, through cell contact or short-distance interactions, induce the metanephric mesenchyme to convert, to epithelia and begin the process of tubulogenesis. To identify new molecules that are involved in these processes, we generated a panel of monoclonal antibodies (MAbs) to the surface of induced mesenchymal cells taken from a day 15 rat embryonic kidney rudiment. MAbs were chosen for further study based either on a distinctive pattern of expression of their antigens or their functional effect on tubulogenesis. We identified a set of MAbs that preferentially stained the glomerular crevice, the first site for formation of the glomerular anlage. Another MAb inhibited tubulogenesis by producing widespread apoptosis in induced mesenchymal cells. This approach promises to identify new molecules that are central to kidney development.

Smad expression during kidney development

2004 ◽  
Vol 286 (4) ◽  
pp. F625-F633 ◽  
Author(s):  
P. Vrljicak ◽  
D. Myburgh ◽  
A. K. Ryan ◽  
M. A. van Rooijen ◽  
C. L. Mummery ◽  
...  
Keyword(s):  
Cell Fate ◽  
Kidney Development ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Mesenchymal Cells ◽  
Ureteric Bud ◽  
Temporal Expression ◽  
The Common ◽  
Nephrogenic Zone

Signaling by the transforming growth factor (TGF)-β superfamily is important during kidney development. Here, we describe the spatial and temporal expression patterns of the Smads, the transcription factors that translate TGF-β signals into gene expression. RT-PCR data and in situ hybridization analysis showed that the receptor-regulated (R) Smads (Smad1, -2, -3, -5, and -8), the common partner Smad (Smad4), and the inhibitory (I) Smads (Smad6 and -7) were all expressed during mouse kidney development from embryonic day 12 until the end of nephrogenesis at postnatal day 15. Each Smad had a distinct spatial distribution. All were expressed by mesenchymal cells in the nephrogenic zone and were downregulated once these cells began to epithelialize. The common partner Smad, Smad4, was present in uninduced mesenchymal cells and at ureteric bud tips. The bone morphogenetic-responsive R-Smads, Smad1, -5, and -8, were mainly expressed in the nephrogenic zone, whereas the TGF-β- responsive R-Smads were predominantly noted in the medullary interstitium. Expression of the I-Smad Smad7 was also seen in mesenchymal cells in the interstitium. Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development.

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 Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development

Development ◽  
2001 ◽  
Vol 128 (16) ◽  
pp. 3105-3115 ◽  
Author(s):  
Ryuichi Nishinakamura ◽  
Yuko Matsumoto ◽  
Kazuki Nakao ◽  
Kenji Nakamura ◽  
Akira Sato ◽  
...  
Keyword(s):  
Kidney Development ◽  
Perinatal Period ◽  
Homozygous Deletion ◽  
Homeotic Gene ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Mouse Homolog ◽  
Tubule Formation ◽  
Murine Homolog ◽  
Inductive Signal

SALL1 is a mammalian homolog of the Drosophilaregion-specific homeotic gene spalt (sal); heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We have isolated a mouse homolog of SALL1 (Sall1) and found that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. Sall1 is expressed in the metanephric mesenchyme surrounding ureteric bud; homozygous deletion ofSall1 results in an incomplete ureteric bud outgrowth, a failure of tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This phenotype is likely to be primarily caused by the absence of the inductive signal from the ureter, as the Sall1-deficient mesenchyme is competent with respect to epithelial differentiation. Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development.

Regulation of BMP7 expression during kidney development

Development ◽  
1998 ◽  
Vol 125 (17) ◽  
pp. 3473-3482 ◽  
Author(s):  
R.E. Godin ◽  
N.T. Takaesu ◽  
E.J. Robertson ◽  
A.T. Dudley
Keyword(s):  
Wnt Signaling ◽  
Kidney Development ◽  
Tooth Development ◽  
Expression Patterns ◽  
Wnt Signaling Pathway ◽  
Sodium Chlorate ◽  
Bmp Signaling ◽  
Proteoglycan Synthesis ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud

Members of the Bone Morphogenetic Protein (BMP) family exhibit overlapping and dynamic expression patterns throughout embryogenesis. However, little is known about the upstream regulators of these important signaling molecules. There is some evidence that BMP signaling may be autoregulative as demonstrated for BMP4 during tooth development. Analysis of BMP7 expression during kidney development, in conjunction with studies analyzing the effect of recombinant BMP7 on isolated kidney mesenchyme, suggest that a similar mechanism may operate for BMP7. We have generated a beta-gal-expressing reporter allele at the BMP7 locus to closely monitor expression of BMP7 during embryonic kidney development. In contrast to other studies, our analysis of BMP7/lacZ homozygous mutant embryos, shows that BMP7 expression is not subject to autoregulation in any tissue. In addition, we have used this reporter allele to analyze the expression of BMP7 in response to several known survival factors (EGF, bFGF) and inducers of metanephric mesenchyme, including the ureteric bud, spinal cord and LiCl. These studies show that treatment of isolated mesenchyme with EGF or bFGF allows survival of the mesenchyme but neither factor is sufficient to maintain BMP7 expression in this population of cells. Rather, BMP7 expression in the mesenchyme is contingent on an inductive signal. Thus, the reporter allele provides a convenient marker for the induced mesenchyme. Interestingly LiCl has been shown to activate the Wnt signaling pathway, suggesting that BMP7 expression in the mesenchyme is regulated by a Wnt signal. Treatment of whole kidneys with sodium chlorate to disrupt proteoglycan synthesis results in the loss of BMP7 expression in the mesenchyme whereas expression in the epithelial components of the kidney are unaffected. Heterologous recombinations of ureteric bud with either limb or lung mesenchyme demonstrate that expression of BMP7 is maintained in this epithelial structure. Taken together, these data indicate that BMP7 expression in the epithelial components of the kidney is not dependent on cell-cell or cell-ECM interactions with the metanephric mesenchyme. By contrast, BMP7 expression in the metanephric mesenchyme is dependent on proteoglycans and possibly Wnt signaling.

Use of conjugates made between a cytolytic T cell clone and target cells to study the redistribution of membrane molecules in cell contact areas

1990 ◽  
Vol 97 (2) ◽  
pp. 335-347
Author(s):  
P. Andre ◽  
A.M. Benoliel ◽  
C. Capo ◽  
C. Foa ◽  
M. Buferne ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Cell Interaction ◽  
Cell Contact ◽  
Computer Assisted ◽  
Target Cells ◽  
Contact Areas ◽  
Surface Molecules ◽  
T Cell Clone ◽  
Cell Cell

In many models of cell-cell adhesion, it was reported that some cell membrane molecules might be redistributed into contact areas. However, this phenomenon was not subjected to precise quantification. In the present work, fluorescence microscopy, immunolabelling and digital image processing were combined to analyse quantitatively the spatial organization of specific or nonspecific conjugates made with a cytolytic T (CTL) lymphocyte clone (BM3.3) and target cells (EL4 or RDM4). Binding was achieved under calcium-free conditions to study the earliest steps of cell interaction, preceding CTL activation. Fluorescent antibodies were used to label class I histocompatibility molecules on both killer and target cells, and T cell receptor, CD3, CD8 and LFA-1 (CD18/CD11a) on the killer cells. Membrane bilayers were stained with a fluorescent phospholipid, glycoconjugates were labelled with periodic oxidation and Lucifer Yellow uptake, and polymerized actin was revealed with a fluorescent phallacidin derivative. Also, the fine geometry of killer-target interaction area was studied with electron microscopy and computer-assisted contour analysis. It is concluded that: (1) qualitative examination of fluorescence photomicrographs cannot permit accurate comparison between different fluorescence densities. (2) The cell-cell contact area was about fourfold higher in specific conjugates than in non-specific ones. (3) The surface density of adhesion molecules exhibited similar increases (between 30 and 80%) in the contact areas of both specific and nonspecific conjugates. (4) However, the amount of redistributed surface molecules was higher when cell-cell interaction was enhanced either by specific immunological recognition (in specific conjugates) or periodate oxidation. (5) Since redistribution did not require extracellular calcium and it was detected on nonspecific conjugates, this did not require full lymphocyte activation. Spatial reorganization of cell surface molecules may thus be a general consequence of adhesion, cell surface mobility and intermolecular forces.

scholarly journals Ureteric Bud Cells Programmed from Embryonic Stem Cells Obtain Competence for Secondary Induction in the Kidney

2019 ◽  
Author(s):  
Zenglai Tan ◽  
Aleksandra Rak-Raszewska ◽  
Ilya Skovorodkin ◽  
Seppo J. Vainio
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Drug Testing ◽  
Kidney Development ◽  
Embryonic Stem ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Direct Differentiation ◽  
Kidney Organoids

SUMMARYGeneration of kidney organoids from pluripotent stem cells (PSCs) is regarded as a potentially powerful way to study kidney development, disease, and regeneration. Direct differentiation of PSCs towards renal lineages is well studied, however, most of the studies relates to generation of nephron progenitor population from PSCs. Until now, differentiation of PSCs into ureteric bud (UB) progenitor cells demonstrates limited success. Here, we describe a simple, efficient and reproductive protocol to direct differentiation of mouse embryonic stem cells (mESCs) into UB progenitor cells. The mESC–derived UB cells were able to induce nephrogenesis when placed in the interaction with the primary metanephric mesenchyme (pMM). In generated kidney organoids, the embryonic pMM developed nephron structures and the mESC-derived UB cells formed network of collecting ducts, connected with the nephron tubules. Altogether, our studies established an uncomplicated and reproducible platform for kidney disease modelling, drug testing and regenerative medicine applications.

The metanephric blastema differentiates into collecting system and nephron epithelia in vitro

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3207-3214 ◽  
Author(s):  
J. Qiao ◽  
D. Cohen ◽  
D. Herzlinger
Keyword(s):  
Cell Fate ◽  
Mesenchymal Cells ◽  
Lacz Gene ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Ureteric Buds ◽  
Collecting System ◽  
Metanephric Blastema

The kidney forms from two tissue populations derived from intermediate mesoderm, the ureteric bud and metanephric mesenchyme. It is currently accepted that metanephric mesenchyme is committed to differentiating into nephrons while the ureteric bud is restricted to forming the renal collecting system. To test this hypothesis, we transferred lacZ into pure metanephric mesenchyme isolated from gestation day 13 rat embryos. The fate of tagged mesenchymal cells and their progeny was characterized after co-culture with isolated ureteric buds. When induced to differentiate by the native inducer of kidney morphogenesis, lineage-tagged mesenchymal cells exhibit the potential to differentiate into collecting system epithelia, in addition to nephrons. The fate of cells deriving from isolated ureteric buds was also examined and results of these lacZ gene transfer experiments indicate that the majority of ureteric bud cells differentiate into the renal collecting system. These cell fate studies combined with in situ morphological observations raise the possibility that collecting system morphogenesis in vivo occurs by growth of the ureteric bud and recruitment of mesenchymal cells from the metanephric blastema. Thus, metanephric mesenchyme may be a pluripotent renal stem population.

Canonical WNT signaling during kidney development

2007 ◽  
Vol 293 (2) ◽  
pp. F494-F500 ◽  
Author(s):  
Diana M. Iglesias ◽  
Pierre-Alain Hueber ◽  
LeeLee Chu ◽  
Robert Campbell ◽  
Anne-Marie Patenaude ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Kidney Development ◽  
Wnt Signaling Pathway ◽  
Renal Tubules ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Fetal Kidney ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

The canonical WNT signaling pathway plays a crucial role in patterning of the embryo during development, but little is known about the specific developmental events which are under WNT control. To understand more about how the WNT pathway orchestrates mammalian organogenesis, we studied the canonical β-catenin-mediated WNT signaling pathway in kidneys of mice bearing a β-catenin-responsive TCF/βGal reporter transgene. In metanephric kidney, intense canonical WNT signaling was evident in epithelia of the branching ureteric bud and in nephrogenic mesenchyme during its transition into renal tubules. WNT signaling activity is rapidly downregulated in maturing nephrons and becomes undetectable in postnatal kidney. Sites of TCF/βGal activity are in proximity to the known sites of renal WNT2b and WNT4 expression, and these WNTs stimulate TCF reporter activity in kidney cell lines derived from ureteric bud and metanephric mesenchyme lineages. When fetal kidney explants from HoxB7/GFP mice were exposed to the canonical WNT signaling pathway inhibitor, Dickkopf-1, arborization of the ureteric bud was significantly reduced. We conclude that restricted zones of intense canonical WNT signaling drive branching nephrogenesis in fetal kidney.

scholarly journals OrganIn VitroCulture: What Have We Learned about Early Kidney Development?

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Aleksandra Rak-Raszewska ◽  
Peter V. Hauser ◽  
Seppo Vainio
Keyword(s):  
Regenerative Medicine ◽  
Kidney Development ◽  
Ex Vivo ◽  
Renal Development ◽  
Metanephric Mesenchyme ◽  
Ureteric Bud ◽  
Chemical Inducers ◽  
Open Platform ◽  
Artificial Environment

When Clifford Grobstein set out to study the inductive interaction between tissues in the developing embryo, he developed a method that remained important for the study of renal development until now. From the late 1950s on,in vitrocultivation of the metanephric kidney became a standard method. It provided an artificial environment that served as an open platform to study organogenesis. This review provides an introduction to the technique of organ culture, describes how the Grobstein assay and its variants have been used to study aspects of mesenchymal induction, and describes the search for natural and chemical inducers of the metanephric mesenchyme. The review also focuses on renal development, starting with ectopic budding of the ureteric bud, ureteric bud branching, and the generation of the nephron and presents the search for stem cells and renal progenitor cells that contribute to specific structures and tissues during renal development. It also presents the current use of Grobstein assay and its modifications in regenerative medicine and tissue engineering today. Together, this review highlights the importance ofex vivokidney studies as a way to acquire new knowledge, which in the future can and will be implemented for developmental biology and regenerative medicine applications.

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