ABSTRACT
Basement membranes are the earliest extracellular matrices produced during embryogenesis. They result from synthesis and assembly into a defined supramolecular architecture of several components, including laminins, collagen IV, nidogen, and proteoglycans. In vitro studies have allowed us to propose an assembly model based on the polymerisation of laminin and collagen IV in two separate networks associated together by nidogen. How nucleation of polymers and insolubilisation of the different components into a basement membrane proceed in vivo is, however, unknown. A most important property of several basement membrane components is to provide signals controling the activity of adjacent cells. The transfer of information is
mediated by interactions with cell surface receptors, among them integrins. Mouse genetics has demonstrated that the absence of these interactions is not compatible with development as deletion of either laminin γ1 chain or integrin β1 chain lead to lethality of mouse embryos at the peri-implantation stage. We have used embyoid bodies as a model system recapitulating the early steps of embryogenesis to unravel the respective roles of laminin and β1 integrins in basement membrane formation. Our data show that there is formation of a basal lamina in wild-type, but not in β1-integrin deficient, embryoid bodies. Surprisingly, in the absence of β1 integrins, laminin 1 was not secreted in the extracellular space due to a rapid switch off of laminin α1 chain synthesis which normally drives the secretion of laminin heterotrimers. These results indicate that β1 integrins are required for the initiation of basement membrane formation, presumably by applying a feed-back regulation on the expression of laminin α1 chain and other components of basement membranes.
