In high-turnover tissues, the precise control of stem cell proliferation is essential for tissue homeostasis. In Drosophila, the integrity of the midgut epithelium is maintained by intestinal stem cells (ISCs) but what regulates the proliferation of these cells? Benoît Biteau and Heinrich Jasper now report that EGF receptor (EGFR) signalling maintains the proliferative capacity of ISCs (see p. ). Using clonal analysis, RNAi knockdown and other experimental approaches, the researchers show that the EGF ligand Vein is expressed in the muscle surrounding the intestinal epithelium and that Vein provides a constitutive signal that activates ERK (extracellular signal-regulated kinase) in ISCs. Interestingly, the transcription factor FOS integrates this EGFR/ERK signal with signals mediated by the JNK (Jun N-terminal kinase) pathway in response to stress. The researchers suggest that the visceral muscle acts as a functional niche for ISCs and propose that FOS, by integrating the niche-derived permissive signal with stress-induced instructive signals, adjusts ISC proliferation to environmental conditions.
