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

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