Development, Vol 121, Issue 6 1569-1580, Copyright © 1995 by Company of Biologists

JOURNAL ARTICLES

Developmental biology of the pancreas

JM Slack
Department of Zoology, Oxford University, UK.

The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.
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				V. Cirulli, G. M. Beattie, G. Klier, M. Ellisman, C. Ricordi, V. Quaranta, F. Frasier, J. K. Ishii, A. Hayek, and D. R. Salomon Expression and Function of {alpha}v{beta}3 and {alpha}v{beta}5 Integrins in the Developing Pancreas: Roles in the Adhesion and Migration of Putative Endocrine Progenitor Cells J. Cell Biol., September 18, 2000; 150(6): 1445 - 1460. [Abstract] [Full Text] [PDF]

				P. Jacquemin, S. M. Durviaux, J. Jensen, C. Godfraind, G. Gradwohl, F. Guillemot, O. D. Madsen, P. Carmeliet, M. Dewerchin, D. Collen, et al. Transcription Factor Hepatocyte Nuclear Factor 6 Regulates Pancreatic Endocrine Cell Differentiation and Controls Expression of the Proendocrine Gene ngn3 Mol. Cell. Biol., June 15, 2000; 20(12): 4445 - 4454. [Abstract] [Full Text]

				H.-P. Huang, M. Liu, H. M. El-Hodiri, K. Chu, M. Jamrich, and M.-J. Tsai Regulation of the Pancreatic Islet-Specific Gene BETA2 (neuroD) by Neurogenin 3 Mol. Cell. Biol., May 1, 2000; 20(9): 3292 - 3307. [Abstract] [Full Text]

				D. J. Hill, B. Strutt, E. Arany, S. Zaina, S. Coukell, and C. F. Graham Increased and Persistent Circulating Insulin-Like Growth Factor II in Neonatal Transgenic Mice Suppresses Developmental Apoptosis in the Pancreatic Islets Endocrinology, March 1, 2000; 141(3): 1151 - 1157. [Abstract] [Full Text] [PDF]

				J. M. Slack Stem Cells in Epithelial Tissues Science, February 25, 2000; 287(5457): 1431 - 1433. [Abstract] [Full Text]

				M Sander, L Sussel, J Conners, D Scheel, J Kalamaras, F Dela Cruz, V Schwitzgebel, A Hayes-Jordan, and M German Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas Development, January 12, 2000; 127(24): 5533 - 5540. [Abstract] [PDF]

				M Hebrok, S. Kim, B St Jacques, A. McMahon, and D. Melton Regulation of pancreas development by hedgehog signaling Development, January 11, 2000; 127(22): 4905 - 4913. [Abstract] [PDF]

				V. Schwitzgebel, D. Scheel, J. Conners, J Kalamaras, J. Lee, D. Anderson, L Sussel, J. Johnson, and M. German Expression of neurogenin3 reveals an islet cell precursor population in the pancreas Development, January 8, 2000; 127(16): 3533 - 3542. [Abstract] [PDF]

				T. J. Kieffer and J. Francis Habener The Glucagon-Like Peptides Endocr. Rev., December 1, 1999; 20(6): 876 - 913. [Abstract] [Full Text]

				S. B. Smith, H. C. Ee, J. R. Conners, and M. S. German Paired-Homeodomain Transcription Factor PAX4 Acts as a Transcriptional Repressor in Early Pancreatic Development Mol. Cell. Biol., December 1, 1999; 19(12): 8272 - 8280. [Abstract] [Full Text] [PDF]

				Y. Fujitani, Y. Kajimoto, T. Yasuda, T.-A. Matsuoka, H. Kaneto, Y. Umayahara, N. Fujita, H. Watada, J.-I. Miyazaki, Y. Yamasaki, et al. Identification of a Portable Repression Domain and an E1A-Responsive Activation Domain in Pax4: a Possible Role of Pax4 as a Transcriptional Repressor in the Pancreas Mol. Cell. Biol., December 1, 1999; 19(12): 8281 - 8291. [Abstract] [Full Text] [PDF]

				D. A. Stoffers, R. S. Heller, C. P. Miller, and J. F. Habener Developmental Expression of the Homeodomain Protein IDX-1 in Mice Transgenic for an IDX-1 Promoter/lacZ Transcriptional Reporter Endocrinology, November 1, 1999; 140(11): 5374 - 5381. [Abstract] [Full Text]