Epithelial-mesenchymal interactions in the production of basement membrane components in the gut

Abstract

The production and deposition of extracellular matrix proteins and the cellular origin of type-IV collagen have been analysed immunocytochemically in cocultured or transplanted intestinal epithelial-mesenchymal cell associations. In the first experimental model, rat intestinal endodermal cells were cultured on top of confluent monolayers of rat intestinal or skin fibroblastic cells. Under these conditions, interstitial matrix and basement membrane proteins were deposited within the fibroblastic layer over the whole culture period; interactions between the epithelial cells and the fibroblastic cell population, whatever their organ of origin, were required for the production of the basement membrane. In addition, its formation was progressive as assessed by the shift of a spot-like labelling to a continuous linear pattern at the epithelial-mesenchymal interface, and paralleled epithelial cell differentiation. In the second experimental model, chick-rat epithelial-mesenchymal recombinants developed as intracoelomic grafts were used, and the immunocytochemical detection of a basement membrane protein, type-IV collagen, was performed with species-specific antibodies. The major role of the mesenchyme in the deposition of type-IV collagen is supported by the fact that anti-chick but not anti-mammalian antibodies stained this antigen in chick mesenchyme-rat endoderm recombinants. These observations emphasize the role of tissue interactions in the formation of a basement membrane and show that the mesenchymal compartment is the principal endogenous source of type-IV collagen.