Bone morphogenetic protein guts it out

Bone morphogenetic protein (BMP) signaling reins in stem cell division during intestinal healing, Guo et al. show.

If cells in a fruit fly’s midgut suffer damage—say, from noxious bacteria in the insect’s diet—intestinal stem cells (start to divide and produce replacements. But the fly needs to turn down the process after the injury has healed to prevent overproduction of new cells. BMP might help restrict this proliferation. The BMP pathway is faulty, for example, in the human genetic disorder juvenile polyposis syndrome, which is characterized by a profusion of intestinal polyps.

Guo et al. found that the BMP pathway performs different jobs in different parts of the fly midgut. The central zone of the midgut, which releases acid and functions like a stomach, continually activates BMP signaling, which was essential for renewal of the acid-producing copper cells.

The anterior and posterior portions of the midgut, by contrast, boost BMP signaling only after an injury. In these sections of the intestine, the pathway serves as a brake on stem cell division. For example, the researchers found that flies with defective BMP signaling spawned more cells after intestinal damage than did controls. But when the pathway was overactive, the flies accumulated fewer fresh intestinal cells. The researchers also determined that muscles surrounding the gut release the molecule, decapentaplegic, that triggers the increase in BMP output. The findings suggest that the symptoms of juvenile polyposis syndrome might result from an abnormal response to intestinal injury.