Laminin: the crux of basement membrane assembly

Abstract

Laminin-1 is emerging as the key molecule in early embryonic basement membrane assembly. Here we review recent insights into its functions gained from the synergistic application of genetic and structural methods.

Figure 1.

Schematic drawing of the cross-shaped laminin molecule and selected interaction partners. All proteins are drawn to scale using dimensions obtained from electron micrographs or crystal structures (10-nm scale bar in upper left corner). The cell membrane is represented by a gray bar. Regions of interest are enlarged to show the atomic structure. In the laminin–nidogen complex structure, three laminin residues essential for nidogen binding are marked by red spheres. In the laminin G domain structure, a heparin-binding sequence and a calcium ion involved in binding the α-subunit of DG are marked by red and green spheres, respectively.

Figure 2.

Comparison of peri-implantation development in vivo and cell differentiation in EBs in vitro. Key stages of peri-implantation development (top) and EB differentiation (bottom) are shown schematically. During implantation, ICM cells (pink) form an outer layer of primitive endoderm, which deposits a BM (green). The ICM cells adjacent to the BM differentiate into the columnar epiblast epithelium (yellow), while cells residing deeper within the ICM undergo apoptosis, thereby forming the proamniotic cavity. Cell differentiation in EBs closely recapitulates that of the ICM during the peri-implantation period. Hence, EBs are frequently used to delineate the mechanism(s) of gene mutations resulting in peri-implantation lethality.