Developmental activities of the epidermal growth factor receptor

Abstract

EGF-Rs are encoded by a single gene which produces two main transcripts that are translated and processed into a single polypeptide chain. The membrane-inserted receptor kinase binds EGF or TGF-alpha at high and low affinities, but how these are related to the pleiotropic activities of the EGF-R is unknown. The widespread distribution of fetal EGF-Rs suggests that they have many functions during mammalian development. The stage- and cell type-specific expression of receptors in tissues such as the placenta, together with the localized production of EGF/TGF-alpha, suggests that fetal EGF-Rs have specific activities and roles. The proliferation of the fetal trophoblast and the maternal deciduum is likely to provide the location for a major and necessary role of TGF-alpha and EGF-Rs, which probably act by autocrine and paracrine means to establish the placenta as rapidly as possible. There is evidence that if placental EGF-Rs malfunction, the fetus is at a disadvantage. This could be partly due to poor placental growth and development, as well as a reduced ability of the placenta to perform a barrier function. The murine fertilized egg at preimplantation stages produces a number of growth factors, including TGF-alpha, but the significance of this is still uncertain. It is likely that several fetal and adult tissues produce low amounts of EGF/TGF-alpha for their self-maintenance. The precise roles for the putative EGF/TGF-alpha produced in the brain, kidney, tooth, and various head tissues are also obscure and will be subjects of close scrutiny in the future.