Laminin α5 influences the architecture of the mouse small intestine mucosa

The mammalian intestine displays two distinct patterns of mucosal organization. The small intestine contains mucosal epithelial invaginations ( the crypts of Lieberkuhn) that are continuous with evaginations ( villi) into the lumen. The colon also contains crypts of Lieberkuhn, but its epithelial surface is lined by flat surface cuffs. The epithelial cells of both organs communicate with the underlying mesenchyme through a basement membrane that is composed of a variety of extracellular matrix proteins, including members of the laminin family. The basement membranes of the small intestine and colon contain distinct laminin subtypes; notably, the villus basement membrane is rich in laminin alpha 5. Here, we show that the diminution of laminin a5 in a mouse model led to a compensatory deposition of colonic laminins, which resulted in a transformation from a small intestinal to a colonic mucosal architecture. The alteration in mucosal architecture was associated with reduced levels of nuclear p27Kip1 - a cell- cycle regulator - and altered intestinal epithelial cell proliferation, migration and differentiation. Our results suggest that laminin a5 has a crucial role in establishing and maintaining the specific mucosal pattern of the mouse small intestine.