The endocrine cells of the gastrointestinal epithelium sense the luminal contents and through secretions at their basolateral side signal both to other epithelial cells and to subepithelial cells, including smooth muscle, neurones, and inflammatory cells.¹ Some of the features of these cells are clearly neurone-like and for a time it was thought that during development they might be derived, like enteric neurones, from the neural crest. This now seems unlikely, and instead it is thought that normally they arise from the pluripotent stem cells that also give rise to the other epithelial cell lineages.² However, in some circumstances at least, these cells appear to have the capacity for proliferation, and in extreme cases this gives rise to tumours that are called “neuroendocrine” as they exhibit some of the features of neurones and endocrine cells. There are many similarities between neuroendocrine tumours of the gastrointestinal tract and pancreas. In general, these tumours grow slowly and the reasons for this are unknown. Wimmel and colleagues³ now present evidence that transforming growth factor β (TGFβ) is produced by neuroendocrine tumours and through autocrine and paracrine mechanisms restrains tumour cell proliferation [see page 1308].

There are over a dozen major enteroendocrine cell (EEC) types, most with a restricted distribution along the gut.¹ The cellular mechanisms that normally determine the differentiation of these cells, and …