Epidermal growth factor and transforming growth factor-alpha in the development of epithelial-mesenchymal organs of the mouse.

Taken together, there is a substantial amount of evidence that EGF-like growth factors have a physiological role in organ development and that the action of EGF or TGF-alpha in the development of epithelial-mesenchymal organs is associated with tissue interactions that guide morphogenesis and differentiation. The functions of growth factors in these interactions are not known at present, but they can be speculated in light of recent data. EGF and TGF-alpha might act as paracrine mediators of tissue interactions during organ development, as has been suggested for TGF-beta, which, together with fibroblast growth factor, acts as a morphogen to induce differentiation of embryonic tissue that is normally induced by tissue interactions (Kimelman and Kirschner, 1987). By in situ hybridization, TGF-beta mRNA was shown to be expressed by epithelial cells in many epithelial-mesenchymal organs (Lehnert and Akhurst, 1988), whereas by immunolocalization the TGF-beta protein was found in the mesenchymal stroma (Heine et al., 1987). Although there have been some studies of the localization of EGF and the EGF-R in the embryo, which are discussed in Chapter 1 of this volume, there is a need for more detailed studies of the relative distribution of cells that synthesize the receptor and its ligand at various stages of organogenesis. The use of appropriate cDNA probes and the in situ hybridization technique will enable the localization of sites of EGF or TGF-alpha synthesis in relation to sites of receptor expression in developing organs and thus provide a deeper understanding of how EGF/TGF-alpha coordinates epithelial-mesenchymal interactions throughout development.