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First published online 15 July 2008
doi: 10.1242/jcs.025528

Journal of Cell Science 121, 2493-2502 (2008)
Published by The Company of Biologists 2008
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Research Article

Laminin {alpha}5 influences the architecture of the mouse small intestine mucosa

Zhen X. Mahoney1, Thaddeus S. Stappenbeck2 and Jeffrey H. Miner1,3,*

1 Department of Internal Medicine/Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA
2 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
3 Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA

* Author for correspondence (e-mail: minerj{at}wustl.edu)

Accepted 13 May 2008

The mammalian intestine displays two distinct patterns of mucosal organization. The small intestine contains mucosal epithelial invaginations (the crypts of Lieberkühn) that are continuous with evaginations (villi) into the lumen. The colon also contains crypts of Lieberkühn, 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 {alpha}5 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 {alpha}5 has a crucial role in establishing and maintaining the specific mucosal pattern of the mouse small intestine.

Key words: Basement membrane, Small intestine, Intestinal epithelial cell, Lutheran (Bcam), p27Kip1 (Cdkn1b)


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