Altered synthesis of laminin 1 and absence of basement membrane component deposition in beta 1 integrin-deficient embryoid bodies

Basement membranes are the earliest extracellular matrices produced during embryogenesis. They result from synthesis and assembly into a defined supra molecular 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 TV in two separate networks associated together by nidogen, How nucleation of po lymers and insolubilisation of the different components into a basement mem brane proceed in vivo is, however, unknown. A most important property of se veral basement membrane components is to provide signals controling the act ivity of adjacent cells. The transfer of information is mediated by interac tions 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 gamma 1 chain or integrin beta 1 chain lead to lethality of mouse embryos at the peri-implantation stage. W e have used embyoid bodies as a model system recapitulating the early steps of embryogenesis to unravel the respective roles of laminin and beta 1 int egrins in basement membrane formation, Our data show that there is formatio n of a basal lamina in wild-type, but not in beta 1-integrin deficient, emb ryoid bodies, Surprisingly, in the absence of beta 1 integrins, laminin 1 w as not secreted in the extracellular space due to a rapid switch off of lam inin alpha 1 chain synthesis which normally drives the secretion of laminin heterotrimers. These results indicate that beta 1 integrins are required f or the initiation of basement membrane formation, presumably by applying a feed-back regulation on the expression of laminin alpha 1 chain and other c omponents of basement membranes.