Pancreas Development

The pancreas is a complex organ composed of two different cell populations, exocrine and endocrine. The exocrine component includes acinar and ductal cells that secrete and transport digestive enzymes into the intestine. Exocrine cells make up the majority of the pancreas and are grouped together into acini and a highly branched ductal system. The endocrine portion is composed of four cell types, alpha, beta, delta and PP cells that secrete glucagon, insulin, somatostatin and pancreatic polypeptide hormones into the bloodstream. The endocrine cells account for approximately 4% of the volume of the pancreas and they are grouped together into islets of Langerhans, in which the alpha, delta and PP cells surround the inner core of beta cells (Fig. 2). Although the mature pancreas is a single organ, it is initially derived from separate dorsal and ventral buds. During embryogenesis these two pancreatic buds are specified differently and arise from different regions: the dorsal pancreas from just below the notochord in the region of the stomach, while the ventral pancreas develops adjacent to the liver. Recent work has shown that signals released from both the notochord and endothelial cells are important for proper specification of the dorsal pancreas, while signals released from the cardiac mesoderm affect ventral pancreas development.


In recent years, several developmental pathways have been shown to play a role in pancreas development, including the Notch, Hedgehog, EGF, FGF and TGF-beta pathways. These pathways operate by activating downstream transcription factors that are essential for proper development of the pancreas. These transcription factors can be grouped into four major families, the Pax, Nkx, bHLH and homeobox gene families. Through loss and gain-of-function studies these transcription factors have been shown to play an important role in both development and maintenance of the pancreas. For example, Pax4 and Pax6 are necessary for delta and alpha cell fate specification respectively, while Nkx2.2 and Nkx6.1 are required for terminal differentiation of the beta cell. Another homeobox gene, HlxB9, is essential for dorsal pancreas development. Three of the more important transcription factors are Pdx-1, p48 and Ngn3. They are necessary for proper development of the entire pancreas, exocrine pancreas and endocrine pancreas respectively. In Pdx1 mutant mice the pancreas does not form; in p48 mutant mice only the endocrine cells are specified; and in ngn3 mutant mice only the exocrine portion of the pancreas develops properly. Understanding how the pancreas forms during embryogenesis is important as it will help diagnose, prevent and cure two diseases that affect the pancreas, diabetes mellitus and pancreatic cancer.

Current projects in pancreas development include:

Fig.2 Immunostaining of rat pancreas for Glucagon (top) and Insulin (bottom)