Laminin α5 guides tissue patterning and organogenesis

Abstract

Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5) is one of the most widely distributed LM in the developing and mature organism. Its presence in some basement membranes during embryogenesis is absolutely required for maintenance of basement membrane integrity and thus for proper organogenesis. LMα5 also regulates the expression of genes important for major biological processes, in part by repressing or activating signaling pathways, depending upon the physiological context.

Figure 1. Schematic representation of LMα5 binding sites for its major receptors. Binding sites to known cellular receptors interacting with the LMα5 chain are depicted on the main functional domains LN and LG (LG1-LG5). The LG3 module (*) is indispensable for α3β1 and α6β1 binding; the precise binding site for α6β4 integrin (★) has not been determined.

Figure 2. A diagrammatic summary of the diverse developmental processes in which LM-511 and the basement membranes that contain it are involved. Results from studies of Lama5 mutant mice, transgenic mice, and cells cultured on LMα5-containing substrates reveal roles in organogenesis (left) and early developmental events (right). See text for details.

Figure 3. The LMα5 chain modulates signaling pathways. Three important signaling pathways have been described so far to be modulated by LMα5, as shown by studies of LMα5-null mice, by microarray experiments, or in reporter assays (in vitro or in mice). These include Shh, Wnt/β-catenin and PI3K/Akt pathways in the indicated tissues.