Laminin α5 chain is required for intestinal smooth muscle development

Laminins (comprised of α, β, and γ chains) are heterotrimeric glycoproteins integral to all basement membranes. The function of the laminin α5 chain in the developing intestine was defined by analysing laminin α5^-/- mutants and by grafting experiments. We show that laminin α5 plays a major role in smooth muscle organisation and differentiation, as excessive folding of intestinal loops and delay in the expression of specific markers are observed in laminin α5^-/- mice. In the subepithelial basement membrane, loss of α5 expression was paralleled by ectopic or accelerated deposition of laminin α2 and α4 chains; this may explain why no obvious defects were observed in the villous form and enterocytic differentiation. This compensation process is attributable to mesenchyme-derived molecules as assessed by chick/mouse α5^-/- grafted associations. Lack of the laminin α5 chain was accompanied by a decrease in epithelial α3β1 integrin receptor expression adjacent to the epithelial basement membrane and of Lutheran blood group glycoprotein in the smooth muscle cells, indicating that these receptors are likely mediating interactions with laminin α5-containing molecules. Taken together, the data indicate that the laminin α5 chain is essential for normal development of the intestinal smooth muscle and point to possible mesenchyme-derived compensation to promote normal intestinal morphogenesis when laminin α5 is absent.