Extracellular Matrix and Growth Factors in Salivary Gland Development

Abstract

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.

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

“…Numerous ECM proteins that are important to salivary gland development and differentiation have been identified, 106 and some of these such as laminin-111 21 and perlecan 23 have been incorporated into biomaterials. The inclusion of such matrix cues in PEG hydrogels will enable investigation of the specific effects of these modifications on encapsulated microsphere proliferation, cell composition and differentiation, and secretion of salivary factors.…”

Dynamics of Salivary Gland Morphogenesis

“…Branching morphogenesis also creates other branched organs, such as lungs, kidneys, and mammary and prostate glands (Lu and Werb, 2008;Affolter et al, 2009;Andrew and Ewald, 2010;Costantini and Kopan, 2010;Morrisey and Hogan, 2010). Branching morphogenesis of salivary glands has been studied extensively, providing new insights into oral biology and morphogenesis of other crucial organs (Grobstein, 1953;Melnick and Jaskoll, 2000;Kadoya and Yamashina, 2005;Patel et al, 2006;Tucker, 2007;Gresik et al, 2009;Andrew and Ewald, 2010;Hsu and Yamada, 2010;Larsen et al, 2010;Sequeira et al, 2010).…”

Region‐specific epithelial cell dynamics during branching morphogenesis

“…Murine salivary gland development involves complex three-dimensional branching and tissue remodeling (reviewed by (Melnick and Jaskoll, 2000;Kadoya and Yamashina, 2005;Patel et al, 2006;Tucker, 2007;Gresik et al, 2009;Andrew and Ewald, 2010;Hsu and Yamada, 2010;Larsen et al, 2010;Miletich, 2010;Sequeira et al, 2010;Harunaga et al, 2011).…”