Journal
DIFFERENTIATION
Volume 74, Issue 7, Pages 349-364Publisher
ELSEVIER SCI LTD
DOI: 10.1111/j.1432-0436.2006.00088.x
Keywords
salivary gland; submandibular gland; branching morphogenesis; fibroblast growth factors; extracellular matrix; laminin; collagen; fibronectin; FGF10; FGFR2b; EGF
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Funding
- Intramural NIH HHS Funding Source: Medline
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [ZIADE000707] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [Z01DE000707] Funding Source: NIH RePORTER
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Salivary gland branching morphogenesis involves coordinated cell growth, proliferation, differentiation, migration, apoptosis, and interaction of epithelial, mesenchymal, endothelial, and neuronal cells. The ex vivo analysis of embryonic mouse submandibular glands, which branch so reproducibly and beautifully in culture, is a powerful tool to investigate the molecular mechanisms regulating epithelium-mesenchyme interactions during development. The more recent analysis of genetically modified mice provides insight into the genetic regulation of branching morphogenesis. The review begins, as did the field historically, focusing on the role of the extracellular matrix (ECM), and its components such as glycosaminoglycans, collagens, and laminins. Following sections describe the modification of the ECM by proteases and the role of cell-matrix and cell-cell receptors. The review then focuses on two major families of growth factors implicated in salivary gland development, the fibroblast growth factors (FGFs) and the epidermal growth factors (EGFs). The salivary gland phenotypes in mice with genetic modification of FGFs and their receptors highlight the central role of FGFs during salivary gland branching morphogenesis. A broader section mentions other molecules implicated from analysis of the phenotypes of genetically modified mice or organ culture experiments. The review concludes with speculation on some future areas of research.
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