INTRODUCTION Basement membranes are specialized extracellular matrices that play fundamental roles in tissue development and function. These thin sheet-like structures are produced through complex interactions between the major components laminins, collagen IV, the heparan sulfate proteoglycan perlecan and nidogen

Basement membranes are specialized extracellular matrices that play fundamental roles in tissue development and function. These thin sheet-like structures are produced through complex interactions between the major components laminins, collagen IV, the heparan sulfate proteoglycan perlecan and nidogen (Mayer and Timpl, 1993). Laminins are heterotrimeric crossshaped multidomain molecules composed of three genetically distinct chains (α, β and γ). To date, 14 different laminin isoforms have been identified and the diversity is mainly due to the existence of five different α chains (Miner and Patton, 1999). Conversely, among the three known γ chains, the laminin γ1 chain shows a ubiquitous expression pattern and is found in all laminin isoforms, with the exception of laminin 5 and laminins 12-14 containing the γ2 and γ3 chain, respectively (Miner and Patton, 1999; Koch et al., 1999; Libby et al., 2000). Purification of laminin 1 under non-denaturing conditions demonstrated that nidogen 1 forms a stable complex with laminin (Paulsson et al., 1987). In addition, nidogen 1 has been shown to bind to most of the currently known basement membrane proteins, including perlecan and collagen IV (Timpl and Brown, 1996). The finding, however, that nidogen 1 can mediate the formation of ternary complexes between laminin and collagen IV in vitro (Fox et al., 1991), led to the hypothesis that it is crucial for basement membrane assembly, by connecting the major networks formed by laminins and collagen IV. The precise mechanisms how basement membranes are assembled and how the biological function of the proteins is maintained within the basement membrane in vivo, are still unclear. In particular, the differential sites of synthesis for nidogen and laminin chains in mesenchymal and epithelial tissues, respectively, (Thomas and Dziadek, 1993; Ekblom et al., 1994) argues for the presence of other factors involved in the assembly processes. Recent results obtained by targeted deletion of cell-surface receptors, such as β1 integrins and dystroglycan showed disruption of basement membrane structures (Kreidberg et al., 1996; Williamson et al., 1997; DiPersio et al., 1997; Sasaki et al., 1998; Henry and Campbell, 1998) and emphasize a role for transmembrane complexes in coordinating the spatial and temporal local concentrations of proteins at the sites of basement membrane formation. It is widely believed that basement membranes serve as both structural barriers and as a substrate for cellular interactions. The genetic inactivation of most of the major components has demonstrated that each of the proteins serves specific functions. Though all mutations interfere at specific stages with basement membrane integrity, the underlying mechanisms most probably differ. Mice deficient for perlecan develop normally before they die of heart failure at 10.5 day post coitum (dpc), because of basement membrane instability caused by mechanical stress 2711 Development 129, 2711-2722 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV2850