The nature and identity of the pancreatic -cell precursor has remained elusive for many years. One model envisions an early multihormonal precursor that gives rise to both -and -cells and the other endocrine cell types. Alternatively, -cells have been suggested to arise late, directly from the GLUT2-and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. In this study, we have identified a subset of the PDX1 + epithelial cells that are marked by expression of N e u r o g e n i n 3 (N g n 3 ). N g n 3 , a member of the basic helix-loop-helix (