Further Development 20.3: Insulin-Secreting Pancreatic Cells

The Endoderm: Tubes and Organs for Digestion and Respiration

The association of the pancreatic tissues with blood vessels is critical in the formation of the insulin-secreting cells of the pancreas. Pdx1 appears to act in concert with other transcription factors to form the endocrine cells of the pancreas, the islets of Langerhans (Odom et al. 2004; Burlison et al. 2008; Dong et al. 2008). The exocrine cells (which produce digestive enzymes such as chymotrypsin) and the endocrine cells (which produce insulin, glucagon, and somatostatin) appear to have the same progenitor (Fishman and Melton 2002), and the level of Ptf1a appears to regulate the proportion of cells in these lineages. The exocrine pancreatic cells have higher amounts of Ptf1a (Dong et al. 2008). The islet cells secrete VEGF to attract blood vessels, and these vessels surround the developing islet (Figure 1D).

The endocrine progenitor cells form two populations: the progenitor of the β and δ cells of the islets of Langerhans, and the progenitor of the α and pancreatic polypeptide (PP) cells (PP is a hormone that regulates gut endocrine secretion). By expressing different factors, these two populations acquire mutually exclusive states. The progenitor of the β and δ cells expresses the transcription factor Pax4, while the α/PP progenitor cell expresses Arx. These are mutually exclusive states, so a cell becomes one cell type or the other. If the cell expresses Pax4 (becoming a β/δ progenitor), it has a further choice. If it expresses the gene for MafA, it becomes a β cell that can secrete insulin. If it doesn’t express MafA, it becomes a δ cell (Figure 1).

**Figure 1** Lineage of pancreatic and liver cells. All pancreatic cells express *Pdx1*, distinguishing them from the cells that will become the liver. Within the pancreatic lineage, the *Ngn3*-expressing endocrine progenitor cells give rise to the endocrine lineages, while *Ptf1a*-expressing cells give rise to the exocrine progenitor that makes the ducts and the acinar cells (which secrete digestive enzymes). The endocrine progenitor can give rise to two lineages, one that can form β and δ cells and another that can form α and PP cells. (After J. X. Zhou et al. 2011. *PLOS ONE* 6: e14752.)

Literature Cited

Burlison, J. S., Q. Long, Y. Fujitani, C. V. Wright and M. A. Magnuson. 2008. Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells. Dev. Biol. 316: 74–86.
PubMed Link

Dong, P. D., E. Provost, S. D. Leach and D. Y. Stainier. 2008. Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas. Genes Dev. 22: 1445–1450.
PubMed Link

Fishman, M. P. and D. A. Melton. 2002. Pancreatic lineage analysis using a retroviral vector in embryonic mice demonstrates a common progenitor for endocrine and exocrine cells. Int. J. Dev. Biol. 46: 201–207.
PubMed Link

Odom, D. T. and 12 others. 2004. Control of pancreas and liver gene expression by HNF transcription factors. Science 303: 1378–1381.
PubMed Link

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