Salivary gland development and disease

Abstract

Mammalian salivary glands synthesize and secrete saliva via a vast interconnected network of epithelial tubes attached to secretory end units. The extensive morphogenesis required to establish this organ is dependent on interactions between multiple cell types (epithelial, mesenchymal, endothelial, and neuronal) and the engagement of a wide range of signaling pathways. Here we describe critical regulators of salivary gland development and discuss how mutations in these impact human organogenesis. In particular, we explore the genetic contribution of growth factor pathways, nerve‐derived factors and extracellular matrix molecules to salivary gland formation in mice and humans. WIREs Dev Biol 2015, 4:573–590. doi: 10.1002/wdev.194 This article is categorized under: Signaling Pathways > Global Signaling Mechanisms Vertebrate Organogenesis > From a Tubular Primordium: Branched Birth Defects > Organ Anomalies

Salivary gland stem cells: A review of development, regeneration and cancer

“…During the next 36 h the endothelium becomes continuous and axons extend from the ganglion and travel along the developing ductal system to envelope newly forming end buds, thus forming an integrated organ system (Coughlin, 1975; Knosp et al , 2015; Knox et al , 2010; Kwon et al , 2017). As would be expected from such a heterogeneous structure, many pathways are involved in regulating epithelial branching, including those mediated by growth factors such as FGF, EGF, WNT, Hedgehog, and EDA (reviewed in Mattingly et al , 2015) and neurotransmitters acetylcholine (ACh) (Knox et al , 2010) and vasoactive intestinal protein (VIP) (Nedvetsky et al , 2014). Although we know a great deal about the impact of these signalling pathways in controlling morphogenesis, we are only beginning to understand their impact on progenitor/stem cell behavior.…”

“…Although we know a great deal about the impact of these signalling pathways in controlling morphogenesis, we are only beginning to understand their impact on progenitor/stem cell behavior. Here we will review those pathways known to regulate progenitor cells and point the reader to excellent reviews on pathways regulating tissue morphogenesis (Kwon and Larsen, 2015; Mattingly et al , 2015; Patel and Hoffman, 2014). …”

SOX2 regulates acinar cell development in the salivary gland

“…These cells produce a mucin and/or protein-rich fluid that is transported through an interconnected ductal network to the external surface where it serves multiple roles including the protection and function of the epithelial mucosa. Although there have been extensive studies on the mechanisms of branching morphogenesis (reviewed in Mattingly et al, 2015), the process by which most mammalian exocrine organs develop, very little is known about the mechanisms that control acinar cell development. Moreover, the factors required for the establishment of the acinar lineage in the developing salivary gland are not known.…”

The Hippo pathway effector YAP is an essential regulator of ductal progenitor patterning in the mouse submandibular gland

“…Understanding how epithelial progenitor cells pattern into ducts and acini, and how this is coordinated with ongoing tissue morphogenesis, is one of the central questions in epithelial development. The submandibular gland (SMG) offers a model to study the molecular mechanisms directing epithelial branching morphogenesis and patterning, with distinct synchronized processes of cell proliferation, clefting, differentiation, migration and apoptosis occurring rapidly during embryogenesis (Hauser and Hoffman, 2015; Mattingly et al, 2015). The developing SMG epithelium communicates with neighboring mesenchymal, neuronal and endothelial cells to direct reiterative rounds of bud and duct formation that mature into epithelial domains that mediate the production, transportation, and secretion of saliva (Knosp et al, 2015; Knox et al, 2010; Lombaert et al, 2013; Patel et al, 2011; Steinberg et al, 2005; Wells et al, 2014).…”