Pancreatic organogenesis — developmental mechanisms and implications for therapy (original) (raw)
Wessels, N. K. & Cohen, J. H. Early pancreas organogenesis: morphogenesis, tissue interactions and mass effects. Dev. Biol.15, 237–270 (1967).A detailed analysis of the specification of pancreas, early pancreatic development and the influence of neighbouring tissues such as the mesenchyme. It includes beautiful and informative pictures of the formation of the pancreatic buds. Article Google Scholar
Pictet, R. & Rutter, W. J. in Handbook of Physiology (eds Steiner, D. F. & Frenkel, N.) 25–66 (Williams & Wilkins, Washington DC, 1972). Google Scholar
Edlund, H. Pancreas: how to get there from the gut? Curr. Opin. Cell Biol. 11, 663–668 (1999). ArticleCASPubMed Google Scholar
Sander, M. & German, M. S. The β cell transcription factors and the development of the pancreas. J. Mol. Med.75, 327–340 (1997). ArticleCASPubMed Google Scholar
St-Ogne, L., Wehr, R. & Gruss, P. Pancreas development and diabetes. Curr. Opin. Genet. Dev.9, 295–300 (1999). Article Google Scholar
Shapiro, A. M. et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343, 230–238 (2000). ArticleCASPubMed Google Scholar
Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature371, 606–609 (1994). ArticleCASPubMed Google Scholar
Offield, M. F. et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development122, 983–995 (1996). CASPubMed Google Scholar
Ahlgren, U., Jonsson, J. & Edlund, H. The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in PDX1/IPF1-deficient mice. Development122, 1409–1416 (1996). CASPubMed Google Scholar
Ahlgren, U., Jonsson, J., Jonsson, L., Simu, K. & Edlund, H. β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes. Genes Dev.12, 1763–1768 (1998). ArticleCASPubMedPubMed Central Google Scholar
Li, H., Arber, S., Jessell, T. M. & Edlund, H. Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nature Genet.23, 67–70 (1999). ArticleCASPubMed Google Scholar
Harrison, K. A., Thaler, J., Pfaff, S. L., Gu, H. & Kehrl, J. H. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in _Hlxb9_-deficient mice. Nature Genet.23, 71–75 (1999).References12and13describe the role ofHlxb9during pancreas development. LikeIpf1/Pdx1, Hlxb9is transiently expressed in the early pancreatic buds, and later in development its expression becomes restricted to differentiated β-cells. This study shows that Hlxb9 is required for the initiation of the dorsal pancreatic programme and for ensuring proper endocrine-cell differentiation in the ventral bud. ArticleCASPubMed Google Scholar
Sussel, L. et al. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic β cells. Development125, 2213–2221 (1998). CASPubMed Google Scholar
Sander, M. et al. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas. Development127, 5533–5540 (2000). CASPubMed Google Scholar
Ahlgren, U., Pfaff, S., Jessel, T. M., Edlund, T. & Edlund, H. Independent requirement for ISL1 in the formation of the pancreatic mesenchyme and islet cells. Nature385, 257–260 (1997). ArticleCASPubMed Google Scholar
Sosa-Pineda, B., Chowdhury, K., Torres, M., Oliver, G. & Gruss, P. The Pax4 gene is essential for differentiation of insulin-producing β cells in the mammalian pancreas. Nature386, 399–402 (1997). ArticleCASPubMed Google Scholar
Sander, M. et al. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev.11, 1662–1673 (1997). ArticleCASPubMed Google Scholar
St-Onge, L., Sosa-Pineda, B., Chowdhury, K., Mansouri, A. & Gruss, P. Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas. Nature387, 406–409 (1997). ArticleCASPubMed Google Scholar
Naya, F. J. et al. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev.11, 2323–2334 (1997). ArticleCASPubMedPubMed Central Google Scholar
Gradwohl, G., Dierich, A., LeMeur, M. & Guillemot, F. Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc. Natl Acad. Sci. USA97, 1607–1611 (2000). ArticleCASPubMedPubMed Central Google Scholar
Krapp, A. et al. The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev.12, 3752–3763 (1998).The authors describe a targeted inactivation of the exocrine transcription factor p48, which is the first gene to be described that selectively impairs exocrine pancreatic development. This paper also provides genetic evidence that islet-cell differentiation, but not organization, is independent of exocrine-cell differentiation. ArticleCASPubMedPubMed Central Google Scholar
Pin, C. L., Rukstalis, J. M., Johnson, C. & Konieczny, S. F. The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity. J. Cell Biol.155, 519–530 (2001). ArticleCASPubMedPubMed Central Google Scholar
Boj, S. F., Parrizas. M., Maestro, M. A. & Ferrer, J. A transcription factor regulatory circuit in differentiated pancreatic cells. Proc. Natl Acad. Sci. USA98, 14481–14486 (2001). ArticleCASPubMedPubMed Central Google Scholar
Dukes, I. D. et al. Defective pancreatic β-cell glycolytic signaling in hepatocyte nuclear factor-1α-deficient mice. J. Biol. Chem.273, 24457–24464 (1998). ArticleCASPubMed Google Scholar
Kaestner, K. H., Katz, J., Liu, Y., Drucker, D. J. & Schutz, G. Inactivation of the winged helix transcription factor HNF3α affects glucose homeostasis and islet glucagon gene expression in vivo. Genes Dev. 13, 495–504 (1999). ArticleCASPubMedPubMed Central Google Scholar
Shih, D. Q., Navas, M. A., Kuwajima, S., Duncan, S. A. & Stoffel, M. Impaired glucose homeostasis and neonatal mortality in hepatocyte nuclear factor 3α-deficient mice. Proc. Natl Acad. Sci. USA96, 10152–10157 (1999). ArticleCASPubMedPubMed Central Google Scholar
Sund, N. J. et al. Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia. Genes Dev. 15, 1706–1715 (2001). ArticleCASPubMedPubMed Central Google Scholar
Rausa, F. et al. The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3β in the developing murine liver and pancreas. Dev. Biol.192, 228–246 (1997). ArticleCASPubMed Google Scholar
Landry, C. et al. HNF-6 is expressed in endoderm derivatives and nervous system of the mouse embryo and participates to the cross-regulatory network of liver-enriched transcription factors. Dev. Biol. 192, 247–257 (1997). ArticleCASPubMed Google Scholar
Jacquemin, P. et al. Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3. Mol. Cell. Biol.20, 4445–4454 (2000). ArticleCASPubMedPubMed Central Google Scholar
Golosow, N. & Grobstein, C. Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev. Biol.4, 242–255 (1962). ArticleCASPubMed Google Scholar
Miettinen, P. J. et al. Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development127, 2617–2627 (2000). CASPubMed Google Scholar
Erickson, S. L. et al. ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2- and heregulin-deficient mice. Development124, 4999–5011 (1997). CASPubMed Google Scholar
Cras-Meneur, C., Elghazi, L., Czernichow, P. & Scharfmann, R. Epidermal growth factor increases undifferentiated pancreatic embryonic cells in vitro: a balance between proliferation and differentiation. Diabetes50, 1571–1579 (2001). ArticleCASPubMed Google Scholar
Kato, S. & Sekine, K. FGF–FGFR signaling in vertebrate organogenesis. Cell. Mol. Biol.45, 631–638 (1999). CASPubMed Google Scholar
Szebenyi, G. & Fallon, J. F. Fibroblast growth factors as multifunctional signaling factors. Int. Rev. Cytol.185, 45–106 (1999). ArticleCASPubMed Google Scholar
Le Bras, S., Miralles, F., Basmaciogullari, A., Czernichow, P. & Scharfmann, R. Fibroblast growth factor 2 promotes pancreatic epithelial cell proliferation via functional fibroblast growth factor receptors during embryonic life. Diabetes47, 1236–1242 (1998). ArticleCASPubMed Google Scholar
Miralles, F., Czernichow, P., Ozaki, K., Itoh, N. & Scharfmann, R. Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas. Proc. Natl Acad. Sci. USA96, 6267–6272 (1999). ArticleCASPubMedPubMed Central Google Scholar
Celli, G., LaRochelle, W. J., Mackem, S., Sharp, R. & Merlino, G. Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO J.17, 1642–1655 (1998). ArticleCASPubMedPubMed Central Google Scholar
Ohuchi, H. et al. FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem. Biophys. Res. Commun. 277, 643–649 (2000). ArticleCASPubMed Google Scholar
Bhushan, A. et al. Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development128, 5109–5117 (2001).References38–42show that FGF signalling stimulates pancreatic epithelial proliferation and exocrine differentiation, and that FGFR2b/FGF10 signalling is required for pancreatic epithelial-cell expansion. CASPubMed Google Scholar
Hart, A. W., Baeza, N., Apelqvist, Å. & Edlund, H. Attenuation of FGF-signalling in mouse β-cells leads to diabetes. Nature408, 864–868 (2000).The authors show that the requirement for Fgfr1c- signalling in adult β-cells for maintenance of β-cell function is downstream of Ipf1/Pdx1 function. Reference47provides a model of Fgfr1c signalling in adult β-cells. ArticleCASPubMed Google Scholar
Otonkoski, T. et al. A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic β-cell growth. Endocrinology137, 3131–3139 (1996). ArticleCASPubMed Google Scholar
Miralles, F., Philippe, P., Czernichow, P. & Scharfmann, R. Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat pancreas during embryonic and fetal life. J. Endocrinol. 156, 431–439 (1998). ArticleCASPubMed Google Scholar
Lammert, E., Cleaver, O., & Melton, D. Induction of pancreatic differentiation by signals from blood vessels. Science294, 564–567 (2001).This paper highlights the stimulatory effect of endothelial cells in pancreatic islet-cell generation and proposes a role for VEGF in this process. ArticleCASPubMed Google Scholar
Edlund, H. Factors controlling pancreatic cell differentiation and function. Diabetologia44, 1071–1079 (2001). ArticleCASPubMed Google Scholar
Apelqvist, Å. et al. Notch-signalling controls pancreatic cell differentiation. Nature400, 877–881 (1999). ArticleCASPubMed Google Scholar
Jensen, J. et al. Control of endodermal endocrine development by Hes-1. Nature Genet.24, 36–44 (2000).References21, 48and49provide evidence that, analogous to its role in the nervous system, Notch signalling controls cell differentiation in the pancreas and thatngn3functions as a pro-endocrine gene. Therefore, in the developing pancreas, Notch signalling seems to control the choice between endocrine and exocrine fates, so that a lack of this signalling results in high expression levels ofngn3, promoting the endocrine fate (cells with active Notch signalling adopt the exocrine fate). Absence of ngn3 function results in a selective loss of all pancreatic endocrine cells, confirming the role ofngn3. ArticleCASPubMed Google Scholar
Kim, S. K., Hebrok, M. & Melton, D. A. Notochord to endoderm signalling is required for pancreas development. Development124, 4243–4252 (1997). CASPubMed Google Scholar
Hebrok, M., Kim, S. K. & Melton, D. A. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev.12, 1705–1713 (1998). ArticleCASPubMedPubMed Central Google Scholar
Deutsch, G., Jung, J., Zheng, M., Lora, J. & Zaret, K. S. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development128, 871–881 (2001). CASPubMed Google Scholar
Pictet, R. L., Rall, L. B., Phelps, P. & Rutter, W. J. The neural crest and the origin of the insulin-producing and other gastrointestinal hormone producing cells. Science191, 191–192 (1976). ArticleCASPubMed Google Scholar
Fontaine, J. & Le Douarin, N. M. Analysis of endoderm formation in the avian blastoderm by the use of quail–chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD series. J. Embryol. Exp. Morphol.41, 209–222 (1977). CASPubMed Google Scholar
Lendahl, U., Zimmerman, L. B. & McKay, R. D. CNS stem cells express a new class of intermediate filament protein. Cell23, 585–595 (1990). Article Google Scholar
Hunziker, E. & Stein, M. Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem. Biophys. Res. Commun. 271, 116–119 (2000). ArticleCASPubMed Google Scholar
Zulewski, H. et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes50, 521–533 (2001). ArticleCASPubMed Google Scholar
Lumelsky, N. et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science292, 1389–1394 (2000). Article Google Scholar
Lee, S. H., Lumelsky, N., Studer, L., Auerbach, J. M. & McKay, R. D. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nature Biotechnol. 18, 675–679 (2000). ArticleCAS Google Scholar
Alpert, S., Hanahan, D. & Teitelman, G. Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell53, 295–308 (1988). ArticleCASPubMed Google Scholar
Nakamura, T. et al. Insulin production in a neuroectodermal tumor that expresses islet factor-1, but not pancreatic-duodenal homeobox 1. J. Clin. Endocrinol. Metab. 86, 1795–1800 (2001). ArticleCASPubMed Google Scholar
Assady, S. et al. Insulin production by human embryonic stem cells. Diabetes50, 1691–1697 (2001). ArticleCASPubMed Google Scholar
Soria, B. et al. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes49, 157–162 (2000). ArticleCASPubMed Google Scholar
Selander, L. & Edlund, H. Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech. Dev.113, 189–192 (2002).The authors show that the intermediate filament protein nestin is expressed in mesenchymal cells of the gastrointestinal tract, including the pancreas, and not in pancreatic progenitor cells, nor in differentiated pancreatic cell types. ArticleCASPubMed Google Scholar
Githens, S. The pancreatic duct cell: proliferative capabilities, specific characteristics, metaplasia, isolation, and culture. J. Pediatr. Gastroenterol. Nutr. 7, 486–506 (1988). ArticleCASPubMed Google Scholar
Rosenberg, L. In vivo cell transformation: neogenesis of β cells from pancreatic ductal cells. Cell Transplant.4, 371–383 (1995). CASPubMed Google Scholar
Bouwens, L. Transdifferentiation versus stem cell hypothesis for the regeneration of islet β-cells in the pancreas. Microsc. Res. Tech.43, 332–336 (1998). ArticleCASPubMed Google Scholar
Stoffers, D. A., Ferrer, J., Clarke, W. L. &. Habener, J. F. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nature Genet.17, 138–139 (1997). ArticleCASPubMed Google Scholar
Hattersley, A. T. Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity. Diabetes Med.15, 15–24 (1998). ArticleCAS Google Scholar
Malecki, M. T. et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nature Genet.23, 323–328 (1999). ArticleCASPubMed Google Scholar
Slack, J. M. Developmental biology of the pancreas. Development121, 1569–1580 (1995). CASPubMed Google Scholar