Transforming growth factor-β: multifunctional regulator of differentiation and development

Abstract

Transforming growth factors-β (TGF-β) are 25 kilodalton (kDa) homodimeric peptides with multifunctional actions controlling the growth, differentiation and function of a broad range of target cells of both epithelial and mesenchymal derivation. They are expressed early in embryogenesis and their tissue-specific and developmentally dependent expression is strongly suggestive of an essential role in particular morphogenetic and histogenetic events. Five distinct TGF-βs have been characterized so far, with 65-80 % homology to each other. By using both molecular biological and immunohistochemical techniques, we are currently attempting to define specific sites of expression of the different TGF-βs and to determine whether TGF-βs 1-5 might have unique functions in development and in the mature organism. Comparative study of the promoter regions for the different TGF-βs and for any particular TGF-β in different species is also underway. Mechanistically, TGF-βs act to control gene expression of their target cells, many of their actions converging on a complex, multifaceted scheme of control of matrix proteins and their interactions with cells; these effects on matrix are thought to mediate many of the effects of TGF-β on development.