Loss of Apc, a tumor suppressor gene conserved from flies to mammals, results in gastrointestinal tumour initiation in humans. Now, on p. 2255, Craig Micchelli and colleagues identify an intriguing novel role for Apc in regulating the proliferation of Drosophila intestinal stem cells(ISCs). The authors demonstrate that reducing Apc function interferes with midgut homeostasis and leads to hyperplasia and multilayering of the midgut epithelium. Inducing small groups of labelled cells that lack Apc function in the adult midgut reveals that Apc is required specifically in the midgut ISC lineage for homeostasis. Apcloss does not affect ISC self-renewal or fate specification, but does increase ISC proliferation. In addition, activating Wnt signalling in ISCs results in phenotypes similar to those caused by Apc mutations, whereas reducing Wnt signalling suppresses the hyperplasia triggered by the loss of Apc. Based on these data, the authors conclude that Wnt signalling partly mediates the effects of Apc, and propose that Drosophila ISCs might be a useful model for investigating gastrointestinal tumour initiation.

2009