Cell signaling regulation in salivary gland development

Abstract

The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review focuses on research conducted on mammalian salivary gland development, particularly on the differentiation of acinar, ductal, and myoepithelial cells. We discuss recent studies that provide conceptual advances in the understanding of the molecular mechanisms of salivary gland development. In addition, we describe the organogenesis of submandibular glands (SMGs), model systems used for the study of SMG development, and the key signaling pathways as well as cellular processes involved in salivary gland development. The findings from the recent studies elucidating the identity of stem/progenitor cells in the SMGs, and the process by which they are directed along a series of cell fate decisions to form functional glands, are also discussed. Advances in genetic tools and tissue engineering strategies will significantly increase our knowledge about the mechanisms by which signaling pathways and cells establish tissue architecture and function during salivary gland development, which may also be conserved in the growth and development of other organ systems. An increased knowledge of organ development mechanisms will have profound implications in the design of therapies for the regrowth or repair of injured tissues. In addition, understanding how the processes of cell survival, expansion, specification, movement, and communication with neighboring cells are regulated under physiological and pathological conditions is critical to the development of future treatments.

Keywords: Cell signaling; Development; Morphogenesis; Salivary gland; Submandibular glands.

Fig. 1

Diagrams of salivary gland development. Oral epithelium is thickened (pre-bud stage) and invaginates into the mesenchyme. The initial bud further proliferates and elongates (initial bud stage) and then stars branching to form multi-end buds (pseudoglandular stage). At the ducts, lumens are formed at the center of bilayers and differentiates into terminal buds (canalicular stage and terminal bud stage)

Fig. 2

A diagram of salivary glands. The salivary glands include collecting, striated, and intercalated duct cells in the duct and acinar (serous and mucous) and myoepithelial cells in the acini. Striated duct exhibit basal striation containing numerous mitochondria. Serous and mucous acinar cells contain numerous secretory granules in the cells

Fig. 3

Schematic images of FGF signaling during salivary gland development

Fig. 4

Schematic images of EGF signaling during salivary gland development

Fig. 5

Schematic images of TGFβ signaling during salivary gland development

Fig. 6

Interaction of parasympathetic nerve system and salivary gland development