The endocrine cells of the pancreas are organized in islet-like structures of α-, β-, δ, and pp-cells, and represent only 2 percent of total pancreas volume. The four hormone-secreting cell types act in concert as major regulators of glucose homeostasis. Establishment and maintenance of the differentiated islet phenotype requires the highly regulated expression of a set of signal transducing elements and transcription factors that induce a specific sequence of morphological transformations. Endodermal epithelial cells make the earliest commitment to pancreas formation during embryonic development by budding-off from the primitive duodenum as progenitor-cells of the pancreatic ductal cells. Progressive budding finally results in the branched structure of the pancreas. While acini and ducts are histologically differentiated in mouse embryos of 14.5 days old (E14.5), endocrine cells appear at E9.5. At that stage the endocrine cells are individually scattered throughout the developing organ. Despite recent breakthroughs, still little is known about the molecular background behind the intrinsic signals in development of these hormone-positive cells. In murine embryos of 9.5 days old (E9.5), the cells that make up the dorsal and ventral pancreatic buds express the homeobox gene PDX-1, the earliest islet/duodenum-specific gene that is presently known.
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