title: Importance of nidogen binding to laminin gamma1 for branching epithelial morphogenesis of the submandibular gland.
abstract: Epithelial-mesenchymal interactions are major driving forces for the development of most solid organs. The importance of these interactions was first shown for the embryonic submandibular gland more than 40 years ago. We here present evidence that interactions between two basement membrane components, nidogen (entactin) and laminin gamma1 chain, could be important for epithelial-mesenchymal interactions in this gland. Nidogen mRNA was detected by in situ hybridization in the mesenchyme, and yet the protein was detected in epithelial and endothelial basement membranes. The role of nidogen-laminin interactions for epithelial morphogenesis was studied by applying antibodies to submandibular gland organ cultures. Antibodies reacting strongly with the nidogen-binding site of laminin gamma1 chain drastically perturbed branching epithelial morphogenesis. Electron microscopy of the epithelial-mesenchymal interface showed that blocking antibodies disrupted the formation of the basement membrane. Epidermal growth factor was shown to increase the expression of nidogen in mesenchyme, and could counteract the effect of the blocking antibodies. We suggest that nidogen could be an important mesenchymal factor for submandibular gland development.
authors.affiliation: Department of Animal Physiology, Uppsala University, Biomedical Center,Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Kadoya
authors.forename: K
authors.initials: K
authors.lastname: Salmivirta
authors.forename: J F
authors.initials: JF
authors.lastname: Talts
authors.forename: K
authors.initials: K
authors.lastname: Kadoya
authors.forename: U
authors.initials: U
authors.lastname: Mayer
authors.forename: R
authors.initials: R
authors.lastname: Timpl
authors.forename: P
authors.initials: P
authors.lastname: Ekblom
mesh_terms: D000818:Animals; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D007797:Laminin / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D009024:Morphogenesis; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D013363:Submandibular Gland / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D007797:Laminin; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C089141:laminin gamma 1; C029967:nidogen; D004815:Epidermal Growth Factor