Information de reference pour ce titreAccession Number: | 00006056-199703270-00026.
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Author: | Sosa-Pineda, Beatriz; Chowdhury, Kamal; Torres, Miguel; Oliver, Guillermo; Gruss, Peter
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Institution: | Max Planck Institute for Biophysical Chemistry, Am Fassberg 37077 Gottingen, Germany. (Sosa-Pineda, Torres, Oliver) Present addresses: Department of Genetics, St Jude Children's Research Hospital, 332 North Lauderdale, P. O. Box 318, Memphis, Tennessee 38101-0318, USA (B.S.-P and G.O.); Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia, Universidad Autonoma, Madrid 28049, Spain (M.T.).
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Title: | The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas.[Letter]
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Source: | Nature. 386(6623):399-402, March 27, 1997.
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Abstract: | The mammalian pancreas contains two distinct cell populations: endocrine cells which secrete hormones into the bloodstream, and exocrine cells, which secrete enzymes into the digestive tract. The four endocrine cell types found in the adult pancreas-alpha, beta, delta and PP-synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. All of these endocrine cells arise from common multipotent precursors, which coexpress several hormones when they start to differentiate. Expression of some homeobox genes in the early developing pancreas has been reported. The Pax4 gene is expressed in the early pancreas, but is later restricted to beta cells. Inactivation of Pax4 by homologous recombination results in the absence of mature insulin- and somatostatin-producing cells (beta and delta, respectively) in the pancreas of Pax4 homozygous mutant mice, but glucagon-producing alpha cells are present in considerably higher numbers. We propose that the early expression of Pax4 in a subset of endocrine progenitors is essential for the differentiation of the beta and delta cell lineages. A default pathway would explain the elevated number of alpha cells in the absence of Pax4.
(C) 1997 Macmillan Magazines Ltd.
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References: | 1. Slack, J. M. W. Developmental biology of the pancreas. Development 121, 1569-1580 (1995).
2. Pictet, R. L. An ultrastructural analysis of the developing embryonic pancreas. Dev. Biol. 29, 436-467 (1972).
3. Alpert, S., Hanahan, D. & Teitelman, G. Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53, 295-308 (1988).
4. Oliver, G. et al. Prox 1, a prospeo-elated homeobox gene expressed uring mouse development. Mech. Dev. 44, 3-16 (1993).
5. Raju, K. et al. Characterization and developmental expression of Tlx-1, the murine homolog of Hox11. Mech. Dev. 44, 51-64 (1993).
6. Turque, N., Plaza, S., Radvanyi, F., Carriere, C. & Saule, S. Pax-QNR/Pax-6, a paired box- and homeobox-containing gene expressed in neurons, is also expressed in pancreatic endocrine cells. Mol. Endocrinol. 8, 929-938 (1994).
7. Wright, C. V. E., Schnegelsberg, P. & De Robertis, E. M. XIHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development 104, 787-794 (1988).
8. Walther, C. et al. Pax: a murine multigene family of paired box-containing genes. Genomics 11, 424-434 (1991).
9. Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. Insulin-promoter factor 1 is required for pancreas development in mice. Nature 371, 606-609 (1994).
10. Offield, M. F. et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122, 983-995 (1996).
11. Guz, Y. et al. Expression of murine STF-1, a putative insulin gene transcription factor, in beta-cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121, 11-18 (1995).
12. Ohlsson, H., Karlsson, K. & Edlund, T. IPF1, a homeo-domain containing transactivator of the insulin gene. EMBO J. 13, 1145-1158 (1994).
13. Miller, C. P., McGehee, R. E. & Habener, J. F. IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J. 13, 1145-1156 (1994).
14. Teitelman, G., Alpert, S., Polak, J. M., Martinez, A. & Hanahan, D. Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118, 1031-1039 (1993).
15. Githens, S. in The Pancreas: Biology, Pathobiology, and Disease 2nd edn (ed. V. L. W. Go et al.) 21-73 (Raven, New York, 1993).
16. Gittes, G. K. & Rutter, W. J. Onset of cell-specific gene expression in the developing mouse pancreas. Proc. Natl Acad. Sci. USA 89, 1128-1132 (1992).
17. Serup, P. et al. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1. Proc. Natl Acad. Sci. USA 93, 9015-9020 (1996).
18. Oliver, G., Wright, C. V. E., Hardwicke, J. & De Robertis, E. M. Differential antero-posterior expression of two proteins encoded by a homeobox gene in Xenopus and mouse embryos. EMBO J. 7, 3199-3209 (1988). (Author: Vol. no. OK?)
19. Dent, J. A., Polson, A. G. & Klymkowsky, M. W. A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus. Development 105, 61-74 (1989).
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Language: | English.
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Document Type: | Letter to Nature.
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Journal Subset: | Life Sciences. Physical Science & Engineering.
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ISSN: | 0028-0836
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NLM Journal Code: | 0410462, nsc
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