Figure 2. Simplified model of the embryological development of islet endocrine cells (reviewed in ref. 21). Stem/progenitor (Stem/Prog) cells arise from the primitive undifferentiated epithelium of the gut tube and express the transcription factor Pdx-1, a master regulator of pancreas development. The endocrine lineage appears soon after and is characterized by the pro-endocrine transcription factor Ngn3. The earliest endocrine cells, pro-α-cells, identified in early development express the proglucagon gene and the prohormone convertase PC1/3 resulting in the production of GLP-1. The division of lineages into α- and β-cells is determined by the relative expression levels of the transcription factors Arx and Pax4. Mature α-cells express PC2 resulting in the production of glucagon. Fully-differentiated β-cells express the insulin gene and produce insulin. GLP-1 is proposed to be a growth factor important for the expansion of pro-α-cells Glucagon, produced late in α-cell development, is proposed to inhibit the growth of pro-α-cells.