Embryonic kidney in organ culture

Saxén, Lauri; Lehtonen, Eero

doi:10.1111/j.1432-0436.1987.tb00176.x

Cited by 93 publications

(51 citation statements)

References 25 publications

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“…This was accomplished using a soluble form of rat RET containing the RET extracellular domain fused to the hinge and CH2 and CH3 regions of the human IgG1 heavy chain. The purified rat RET-Ig fusion protein was active in a fetal kidney organ culture assay (14,15), where RET is essential for the growth and branching of the ureteric bud epithelium that gives rise to the collecting ducts. A clear reduction in the overall size and the degree of branching of the collecting ducts was seen in RET-Ig treated kidneys (data not shown), indicating that the fusion protein blocked RET signaling.…”

Section: Resultsmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins

Sanicola

Hession

Worley

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

274

194

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Glial cell line-derived neurotrophic factor (GDNF)-dependent activation of the tyrosine kinase receptor RET is necessary for kidney and enteric neuron development, and mutations in RET are associated with human diseases. Activation of RET by GDNF has been shown to require an accessory component, GDNFR-␣ (RETL1). We report the isolation and characterization of rat and human cDNAs for a novel cell-surface associated accessory protein, RETL2, that shares 49% identity with RETL1. Both RETL1 and RETL2 can mediate GDNF dependent phosphorylation of RET, but they exhibit different patterns of expression in fetal and adult tissues. The most striking differences in expression observed were in the adult central and peripheral nervous systems. In addition, the mechanisms by which the two accessory proteins facilitate the activation of RET by GDNF are quite distinct. In vitro binding experiments with soluble forms of RET, RETL1 and RETL2 demonstrate that while RETL1 binds GDNF tightly to form a membrane-associated complex which can then interact with RET, RETL2 only forms a high affinity complex with GDNF in the presence of RET. This strong RET dependence of the binding of RETL2 to GDNF was confirmed by FACS analysis on RETL1 and RETL2 expressing cells. Together with the recent discovery of a GDNF related protein, neurturin, these data raise the possibility that RETL1 and RETL2 have distinctive roles during development and in the nervous system of the adult. RETL1 and RETL2 represent new candidate susceptibility genes and͞or modifier loci for RETassociated diseases.

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Section: Resultsmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins

Sanicola

Hession

Worley

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

274

194

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“…9,24 Address correspondence to W. W. Minuth, Department of Molecular and Cellular Anatomy, University of Regensburg, University Street 31, D-93053 Regensburg, Germany. Electronic mail: will.minuth@vkl.uni-regensburg.de Annals of Biomedical Engineering, Vol.…”

Section: Introductionmentioning

confidence: 99%

“…9,24 In these transfilter experiments both tissues were coated by agarose. During culture in medium containing serum the interaction between both tissues through the pores results in the development of tubules within the mesenchyme.…”

Section: Introductionmentioning

confidence: 99%

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

et al. 2010

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Abstract-An increasing number of investigations is dealing with the repair of acute and chronic renal failure by the application of stem/progenitor cells. However, accurate data concerning the cell biological mechanisms controlling the process of regeneration are scarce. For that reason new implantation techniques, advanced biomaterials and morphogens supporting regeneration of renal parenchyma are under research. Special focus is directed to structural and functional features of the interface between generating tubules and the surrounding interstitial space. The aim of the present experiments was to investigate structural features of the interstitium during generation of tubules. Stem/ progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of a polyester fleece to create an artificial interstitium. Perfusion culture was performed for 13 days in chemically defined Iscove's Modified Dulbecco's Medium containing aldosterone (1 9 10 À7 M) as tubulogenic factor. Recordings of the artificial interstitium in comparison to the developing kidney were performed by morphometric analysis, scanning and transmission electron microscopy. The degree of differentiation was registered by immunohistochemistry. The data reveal that generated tubules are embedded in a complex network of fibers consisting of newly synthesized extracellular matrix proteins. Morphometric analysis further shows that the majority of tubules within the artificial interstitium develops in a surprisingly close distance between 5 and 25 lm to each other. The abundance of synthesized extracellular matrix acts obviously as a spacer keeping generated tubules in distance. For comparison, the same principle of construction is found in the developing parenchyma of the neonatal kidney. Most astonishingly, scanning electron microscopy reveals that the composition of interstitial matrix is not homogeneous but differs along a cortico-medullary axis of proceeding tubule development.Keywords-Tissue engineering, Perfusion culture, Kidney, Tubule, Artificial interstitium, Collagen type III. INTRODUCTIONRecovery from renal failure requires the replacement of injured tissue with new cells that restore epithelial integrity and functionality within tubules. An increasing number of papers is therefore dealing with strategies for repair of parenchyma by the help of stem/progenitor cells. 5,12 However, recent data show that an effective therapy is still far away from a widespread clinic application. Unsolved issues in renal tissue engineering are the concentration of stem/progenitor cells at the site of damage, their integration in a diseased environment, the process of differentiation into nephron-specific cells, and the spatial development of tubules within the kidney. 32 Part of actual research is focusing on cell biological mechanisms involved in the formation of tubules during regeneration. 4 Due to the spatial microarchitecture of the kidney experiments are frequently performed applying three-dimensional culture experiments in combination wi...

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“…All four Notch molecules undergo intramembrane proteolysis (Mizutani et al, 2001;Saxena et al, 2001). To investigate the role of Notch signaling in kidney development without the problems associated with early embryonic lethality (Gridley, 1997) and functional redundancy, we combined a pharmacological approach with metanephric organ culture (Rogers et al, 1991;Saxen and Lehtonen, 1987). By culturing metanephroi in the presence of the γ-secretase inhibitor DAPT (Dovey et al, 2001), we have been able to block all γ-secretase activity -and therefore all Notch signaling -and record the consequences for kidney development.…”

Section: Introductionmentioning

confidence: 99%

γ-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney

et al. 2003

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Notch signaling is involved in pronephros development inXenopus and in glomerulogenesis in mice. However, owing to early lethality in mice deficient for some Notch pathway genes and functional redundancy for others, a role for Notch signaling during early stages of metanephric development has not been defined. Using an antibody specific to the N-terminal end of γ-secretase-cleaved Notch1, we found evidence for Notch1 activation in the comma and S-shaped bodies of the mouse metanephros. We therefore cultured mouse metanephroi in the presence of a γ-secretase inhibitor, N-S-phenyl-glycine-t-butyl ester (DAPT), to block Notch signaling. We observed slightly reduced ureteric bud branching but normal mesenchymal condensation and expression of markers indicating that mesenchyme induction had occurred. However, fewer renal epithelial structures were observed, with a severe deficiency in proximal tubules and glomerular podocytes, which are derived from cells in which activated Notch1 is normally present. Distal tubules were present but in reduced numbers, and this was accompanied by an increase in intervening, non-epithelial cells. After a transient 3-day exposure to DAPT, proximal tubules expanded, but podocyte differentiation failed to recover after removal of DAPT. These observations suggest that γ-secretase activity, probably through activation of Notch, is required for maintaining a competent progenitor pool as well as for determining the proximal tubule and podocyte fates.Supplemental data available online

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Embryonic kidney in organ culture

Cited by 93 publications

References 25 publications

Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins

Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

γ-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney

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