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Table of Contents
Vol. 6, No. 4, 1998
Issue release date: July – August
Section title: Original Paper
Exp Nephrol 1998;6:337–351
(DOI:10.1159/000020541)

Glial Cell Line-Derived Neurotrophic Factor Stimulates Ureteric Bud Outgrowth and Enhances Survival of Ureteric Bud Cells in vitro

Towers P.R.a · Woolf A.S.a,b · Hardman P.a,c
a Developmental Biology and b Nephrourology Units, Division of Cell and Molecular Biology, Institute of Child Health, University College London, and c Division of Cell Sciences, University of Southampton, School of Biological Sciences, Southampton, UK

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: July 15, 1998
Issue release date: July – August

Number of Print Pages: 15
Number of Figures: 0
Number of Tables: 0

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE

Abstract

Development of epithelial organs requires co-ordinated interactions between epithelial and mesenchymal tissues. Studies using null mutant mice have indicated that the ret receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF), are crucial for initiation of development of the metanephric kidney. However, the role of this signalling system in other branching organs has not been analysed. Here we describe detailed expression studies of ret, GDNF, and a co-receptor for GDNF (GDNFRα) in the developing mouse metanephros, lung, and submandibular salivary gland. Also, we examined the role of this signalling system in the development of these organs in vitro. In situ hybridisation revealed differences in the spatial distribution of the three transcripts in the different organs. At the initiation of metanephric development, late on embryonic day 10 (E10), ret and GDNFRα were detected in the Wolffian duct (including the presumptive ureteric bud) whilst the presumptive metanephric mesenchyme expressed GDNFRα and GDNF. Later in development, all three transcripts were restricted to the nephrogenic zone. In contrast, expression in the lung was not detectable by in situ hybridisation until after initiation of development, at E13.5. At this time ret was expressed throughout the epithelium; GDNF was detected throughout the mesenchyme, and GDNFRα was present in the proximal epithelium and mesenchyme only. Ret and GDNF were not detected in the epithelium or mesenchyme of the developing salivary gland, however, GDNFRα was expressed in the mesenchyme at E13.5 and E16.5. Functional studies demonstrated that in organ culture, GDNF significantly increased branching morphogenesis of the E11.5 metanephros, and induced the formation of ectopic ureteric buds from the base of the bud and from the Wolffian duct. The development of lung and salivary primordia were not affected under similar growth conditions. In a novel ureteric bud primary culture system, GDNF significantly increased cell numbers at 24 and 48 h. In cells cultured on laminin this increase was due to increased survival and proliferation, whereas in cells cultured on fibronectin, only survival was enhanced. Our data suggest that GDNF stimulates outgrowth of the ureteric bud, in part, by enhancing cell survival and possibly by increasing proliferation.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: July 15, 1998
Issue release date: July – August

Number of Print Pages: 15
Number of Figures: 0
Number of Tables: 0

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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