Basement membrane components and their receptors in organogenesis

Abstract: During embryogenesis organs are formed from epithelial and mesenchymal tissues. Organogenesis is dependent on interactions between epithelium and mesenchyme. Specialized extracellular matrices, basement membranes, located between the two tissue types play a crucial role in mediating the interactions. Cell surface receptors such as integrins, bind to the extracellular molecules and mediate signals to cells. Basement, membranes consist mainly of laminin, collagen type IV, nidogen and perlecan. Several isoforms of these basement membrane molecules have been identified. In the present study the expression of different laminin alpha chains, their integrin type receptors, and collagen type IV during mouse embryonic development was investigated. Furthermore, the role of nidogen-1-laminin interaction in salivary gland development was studied and a second isoform of mouse nidogen and its expression during embryogenesis was characterized.The results indicate that both epithelial and mesenchymal cells produce basement membrane components and that the expression patterns are spatio-temporally regulated. Furthermore, a colocalization of laminin α3 and α5 chains with integrin type laminin receptors at the basal side of dental epithelium was shown indicating that they may function together.Mesenchymal factors are known to be required for proper epithelial morphogenesis. Nidogen-1, a laminin binding basement membrane protein produced by mesenchyme has been suggested to play a role in epithelial morphogenesis. It was shown that antibodies blocking the nidogen-1-laminin interaction cause disruption of basement membrane and perturb salivary gland development. This finding suggests that the nidogen-1-laminin interaction is essential for proper basement membrane assembly and epithelial morphogenesis. It was also shown that mouse nidogen-2 and nidogen-1 are 46% identical and have similar domain structure. The embryonic expression of the two proteins were remarkably overlapping. A role for both nidogens in basement membrane assembly is proposed.