Extracellular matrix and growth factors in salivary gland development.

The interstitial extracellular matrix (ECM) and epithelial-cell associated basement membrane (BM) play critical roles in the morphogenesis and differentiation of developing salivary glands. Early studies used ex vivo organ culture and tissue recombination methods to identify the importance of the ECM in organ development. Incorporation of transgenic mice and molecular tools has facilitated progress in our understanding of the mechanisms by which ECM proteins influence SMG development. Recent work has identified alterations in the ECM, BM, and associated proteins in salivary gland diseases, including Sjögren's syndrome and salivary gland cancers, but the significance of such changes is not known. Understanding the basic mechanisms controlling morphogenesis and differentiation in mammalian organ development is the first step towards understanding pathogenesis. Molecular characterization of the function of the ECM and BM in cellular processes is critical for future development of therapeutic approaches in regenerative medicine and tissue engineering. Here we provide a historical overview of experiments defining the functions of the ECM, ECM receptors, and associated molecules in salivary gland development. We include a discussion of the function of ECM-associated proteases and major growth factor signaling components that are in some way regulated by the ECM or associated molecules. We conclude with a discussion of defects in ECM and BM occurring in salivary gland pathologies and speculation on future areas of research pertaining to further understanding of the function of the ECM in the salivary gland.