23 TGF-β Family in Epithelial Development

Abstract

Transforming growth factor-β (TGF-β) family members, such as TGF-βs, activins, inhibins, bone morphogenetic proteins (BMPs), and nodal, have critical roles in the development of epithelial structures in a variety of organs, including the skin, lung, mammary gland, and gastrointestinal tract. These organs consist of cell populations derived from the ectoderm, mesoderm, and/or endoderm. The differentiation and function of cells derived from each of these three germ layers are regulated by TGF-β family members through autocrine and paracrine mechanisms, thus positioning these proteins as key regulators of organogenesis (Weaver et al. 1999; Schier 2003). The effects of TGF-β proteins are subject to autoregulatory interactions that control the activities and propagation of signaling. These effects are restricted temporally and spatially by the expression of ligands, receptors, and soluble ligand inhibitors and postreceptor signaling proteins. The roles of TGF-β family proteins in epithelial development have been deduced primarily from studies of the mammary gland, lung, and gastrointestinal tract, which are derived from the endoderm and mesoderm, and of the skin, which is from ectodermal and mesodermal origin. Furthermore, study of the epidermal appendages, specifically the teeth, hair, and feathers, has contributed to our understanding of the role of TGF-β family members in epithelial development and epithelial–mesenchymal interactions. This chapter discusses the roles of TGF-β family proteins and TGF-β signaling mediators in epithelial development in these organ systems. TGF-β family members affect the epithelium both during embryonic development and in the adult organism. In embryonic development, TGF-β, activin, and BMP-4 regulate some of...