Pancreas - Embryological Development

Embryological Development

The pancreas forms from the embryonic foregut and is therefore of endodermal origin. Pancreatic development begins the formation of a ventral and dorsal anlage (or buds). Each structure communicates with the foregut through a duct. The ventral pancreatic bud becomes the head and uncinate process, and comes from the hepatic diverticulum.

Differential rotation and fusion of the ventral and dorsal pancreatic buds results in the formation of the definitive pancreas. As the duodenum rotates to the right, it carries with it the ventral pancreatic bud and common bile duct. Upon reaching its final destination, the ventral pancreatic bud fuses with the much larger dorsal pancreatic bud. At this point of fusion, the main ducts of the ventral and dorsal pancreatic buds fuse, forming the duct of Wirsung, the main pancreatic duct.

Differentiation of cells of the pancreas proceeds through two different pathways, corresponding to the dual endocrine and exocrine functions of the pancreas. In progenitor cells of the exocrine pancreas, important molecules that induce differentiation include follistatin, fibroblast growth factors, and activation of the Notch receptor system. Development of the exocrine acini progresses through three successive stages. These include the predifferentiated, protodifferentiated, and differentiated stages, which correspond to undetectable, low, and high levels of digestive enzyme activity, respectively.

Progenitor cells of the endocrine pancreas arise from cells of the protodifferentiated stage of the exocrine pancreas. Under the influence of neurogenin-3 and Isl-1, but in the absence of notch receptor signaling, these cells differentiate to form two lines of committed endocrine precursor cells. The first line, under the direction of Pax-0, forms α- and γ- cells, which produce glucagon and pancreatic polypeptides, respectively. The second line, influenced by Pax-6, produces β- and δ-cells, which secrete insulin and somatostatin, respectively.

Insulin and glucagon can be detected in the human fetal circulation by the fourth or fifth month of fetal development.