Each type of pancreatic islet cell produces a different hormone. For example, beta cells produce insulin, whereas alpha cells produce glucagon. In mouse embryos, the transcription factor neurogenin 3 (Ngn3) controls endocrine cell fate decisions in multipotent pancreatic progenitor cells, but how? On p. 203, Josselin Soyer and co-workers identify the winged helix transcription factor Rfx6 as a novel Ngn3-dependent regulator of islet cell development in mice and zebrafish. The researchers show that mouse Rfx6 and its zebrafish ortholog rfx6 are expressed in islet progenitor cells and in all developing and adult islet cell types. Furthermore, loss-of-function experiments in zebrafish indicate that the differentiation of glucagon-, ghrelin- and somatostatin-expressing cells is blocked at the progenitor stage in the absence of Rfx6, whereas insulin-expressing cells differentiate normally but fail to form compact islets. This new information about the Ngn3-controlled genetic program during pancreas development might facilitate efforts to produce functional beta cells from human embryonic stem cells for the treatment of type 1 diabetes.