Epithelial β1 integrins are known for their anchoring abilities. But their talents are different in the gut, say Jones et al. (page 505), where cells without β1 integrin stick just fine but overproliferate.

By anchoring cells to the matrix, β1 integrin probably keeps cells alive and cycling. Indeed, proliferation is promoted, not halted, by this integrin in skin and mammary epithelia. So Jones and colleagues were surprised to find that mouse gut epithelial stem cells were hyperproliferative upon loss of β1 integrin.

Too busy dividing, these stem cells did not differentiate into a proper epithelium. As a result, the mutant mice died soon after birth from a lack of nutrient absorption.

Different receptors must stick these stem cells to their matrix, as the authors found no anchorage or survival problems. Here, β1 integrin appears to be more concerned with signaling; its loss led to a PI3K-dependent decrease in Hedgehog (Hh) expression. The loss of intestinal Hh is known to increase cell proliferation.

Gut epithelial cells lack Hh receptors, so the authors suspect that Hh acts on the surrounding stromal cells, which respond by making molecules such as BMPs that down-regulate epithelial proliferation. The situation is different in the skin and breast, where Hh is both expressed and detected by epithelial cells.