Journal article
Dystroglycan binding to laminin α1LG4 module influences epithelial morphogenesis of salivary gland and lung in vitro
Differentiation (London), Vol.69(2), pp.121-134
2001
DOI: 10.1046/j.1432-0436.2001.690206.x
Abstract
Dystroglycan is a receptor for the basement membrane components laminin-1, −2, perlecan, and agrin. Genetic studies have revealed a role for dystroglycan in basement membrane formation of the early embryo. Dystroglycan binding to the E3 fragment of laminin-1 is involved in kidney epithelial cell development, as revealed by antibody perturbation experiments. E3 is the most distal part of the carboxyterminus of laminin α1 chain, and is composed of two laminin globular (LG) domains (LG4 and LG5). Dystroglycan-E3 interactions are mediated solely by discrete domains within LG4. Here we examined the role of this interaction for the development of mouse embryonic salivary gland and lung. Dystroglycan mRNA was expressed in epithelium of developing salivary gland and lung. Immunofluorescence demonstrated dystroglycan on the basal side of epithelial cells in these tissues. Antibodies against dystroglycan that block binding of α-dystroglycan to laminin-1 perturbed epithelial branching morphogenesis in salivary gland and lung organ cultures. Inhibition of branching morphogenesis was also seen in cultures treated with polyclonal anti-E3 antibodies. One monoclonal antibody (mAb 200) against LG4 blocked interactions between α-dystroglycan and recombinant laminin α1LG4 – 5, and also inhibited salivary gland and lung branching morphogenesis. Three other mAbs, also specific for the α1 carboxyterminus and known not to block branching morphogenesis, failed to block binding of α-dystroglycan to recombinant laminin α1LG4 – 5. These findings clarify why mAbs against the carboxyterminus of laminin α1 differ in their capacity to block epithelial morphogenesis and suggest that dystroglycan binding to α1LG4 is important for epithelial morphogenesis of several organs.
Details
- Title: Subtitle
- Dystroglycan binding to laminin α1LG4 module influences epithelial morphogenesis of salivary gland and lung in vitro
- Creators
- Madeleine Durbeej - Department of Animal Physiology, Uppsala University, Uppsala, SwedenJan F Talts - Section for Cell and Developmental Biology, BMC B12, Department of Cell and Molecular Biology, Lund University, Sölvegatan 19, SE-22184 Lund, Sweden: Tel: +46 46 222 0903, Fax: +46 46 222 0855Michael D Henry - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242 USAPeter D Yurchenco - Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854 USA, M. Durbeej and J. F. Talts contributed equally to this workKevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242 USAPeter Ekblom - Department of Animal Physiology, Uppsala University, Uppsala, Sweden
- Resource Type
- Journal article
- Publication Details
- Differentiation (London), Vol.69(2), pp.121-134
- Publisher
- Elsevier B.V
- DOI
- 10.1046/j.1432-0436.2001.690206.x
- ISSN
- 0301-4681
- eISSN
- 1432-0436
- Language
- English
- Date published
- 2001
- Academic Unit
- Neurology; Pathology; Radiation Oncology; Urology; Iowa Neuroscience Institute; Molecular Physiology and Biophysics
- Record Identifier
- 9984020891502771
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