Developmental expression and cellular origin of the laminin alpha 2, alpha4, and alpha 5 chains in the intestine

Laminins ale extracellular matrix glycoproteins that are involved in variou s cellular functions, including adhesion, proliferation, and differentiatio n. In this study, we examine the expression patterns and the cellular origi ns of the laminin alpha 2, alpha 4, and alpha 5 chains in the developing mo use intestine and in in vitro mouse/chick or chick/mouse interspecies hybri d intestines. In situ hybridization and Northern blot analysis revealed tha t mRNA levels for all three laminin ex chains are highest in the fetal inte stine undergoing intense morphogenetic movements. Laminin alpha 4 mRNA and polypeptide are associated with mesenchyme-derived cell populations such as endothelium and smooth muscle. In contrast, laminin alpha 2 and alpha 5 ch ains participate in the structural organization of the subepithelial baseme nt membrane and, in the mature intestine, show a complementary pattern of e xpression. All three laminin alpha chains occur in the smooth muscle baseme nt membrane, with a differential expression of laminin alpha 5 chain in the circular and longitudinal smooth muscle layers. The cellular origin of lam inin alpha 2 and alpha 5 chains found in the subepithelial cell basement me mbrane was studied by immunocytochemical analysis of mouse/chick or chick/m ouse interspecies hybrid intestines at various stages of development using mouse-specific antibodies. Laminin alpha 2 was found to be deposited into t he basement membrane exclusively by mesenchymal cells, while the laminin al pha 5 chain was deposited by both epithelial and mesenchymal cells in an ap parently developmentally regulated pattern. We conclude that (1) multiple l aminin alpha chains are expressed in the intestine, implying specific roles for individual laminin isoforms during intestinal development, and (2) rec iprocal epithelial/mesenchymal interactions are essential for the formation of a structured subepithelial basement membrane, (C) 1999, Academic Press.