I. In vivo pancreas organogenesis

The pancreas is a compound gland with both exocrine and endocrine functions. The exocrine pancreas consists of acinar and ductal cells, which regulate digestion, while the endocrine pancreas consists of hormone-producing cells: glucagon (α cells), insulin (β cells), somatostatin (δ cells), and pancreatic polypeptide (PP cells). The differentiation in specialized cells consists of a progressive loss of multipotency, as reviewed in Greggio et al (Anne Grapin-Botton lecture).3 Indeed the pancreatic primordia arises from the foregut endoderm, starting from a group of multipotent progenitors expressing the transcription factors PDX1, PTF1a, SOX9, and HNF1b (Figure 1).4 These cells undergo massive proliferation, sustained by active epithelial Notch signaling and initially by mesenchymal FGF10. Progenitors become progressively polarized and organized into a branched tubular system. This morphogenetic process is accompanied by a potency restriction: the PTF1a+ cells at the “tips” of the tubes become irreversibly committed to an acinar fate, while cells in the “trunks” (HNF1b+ and SOX9+) remain bipotent until birth approximately and give rise to both endocrine and ductal cells.