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Gene Review

Pdx1  -  pancreatic and duodenal homeobox 1

Mus musculus

Synonyms: IDX-1, IPF-1, Insulin promoter factor 1, Ipf1, Islet/duodenum homeobox 1, ...
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Disease relevance of Pdx1

  • Mutations affecting the Ipf1 protein may promote diabetes mellitus in mice and humans [1].
  • To explore induced islet neogenesis in the liver as a strategy for the treatment of diabetes, we used helper-dependent adenovirus (HDAD) to deliver the pancreatic duodenal homeobox-1 gene (Ipf1; also known as Pdx-1) to streptozotocin (STZ)-treated diabetic mice [2].
  • Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY [3].
  • We were unable to correct hyperglycemia in mice with streptozotocin-induced diabetes using AAV vectors expressing Pdx-1 and Ngn3 [4].
  • We delivered Pdx-1 and Ngn3 to the livers of diabetic mice using adeno-associated virus (AAV) serotype 8, a vector that has been shown to result in non-toxic, persistent, high level expression of the transgene [4].

Psychiatry related information on Pdx1

  • These results suggest that a congenital or genetic perturbation occurred in this infant most likely before the appearance of dorsal pancreatic bud in the 3 mm long embryonic stage, around the embryonic day 25 in human development, before the onset of Ipf-1 expression [5].

High impact information on Pdx1

  • Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus [1].
  • Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression [6].
  • Pancreas development is known to be abolished in Pdx1-mutant mice and Pax4 mutants lack insulin-producing beta-cells [7].
  • In mouse embryos, IPF1 expression is restricted to the developing pancreatic anlagen and is initiated when the foregut endoderm is committed to a pancreatic fate [8].
  • Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of expression, which was studied in combination with wild-type and protein-null alleles [9].

Chemical compound and disease context of Pdx1


Biological context of Pdx1


Anatomical context of Pdx1

  • The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth [13].
  • Hepatocyte nuclear factors (HNFs) -1alpha, -3beta, -4alpha, and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in beta-cell development and function [16].
  • To test this, we used the promoter of the Ipf1/Pdx1 gene to selectively express Shh in the developing pancreatic epithelium [17].
  • We conclude that RA synthesized in the mesenchyme is specifically required for the normal development of the dorsal pancreatic endoderm at a stage preceding Pdx 1 function [14].
  • Using antisera against recombinant IPF-1 and STF-1 in combination with antisera against islet hormones we find that all beta-cells in monolayers of newborn rat islet cells express STF-1, as do a fraction of the delta-cells [15].

Associations of Pdx1 with chemical compounds


Physical interactions of Pdx1


Regulatory relationships of Pdx1

  • Moreover, HNF-6 could directly stimulate the Pdx1 promoter [24].
  • These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression [11].
  • The pancreas derives from cells in the ventral and dorsal foregut endoderm that express the transcription factor Pdx-1 [24].
  • CONCLUSIONS: Overexpression of TGF-alpha induces expansion of a Pdx1-expressing epithelium characterized by focal expression of Pax6 and initiation of islet neogenesis [25].
  • We have evaluated the hypothesis that increased levels of TGFalpha in the fundus induces an antral pattern of cell differentiation in fundic glands by studying Pdx1, a transcription factor whose expression normally is confined to the gastric antrum [26].
  • Adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription [27].

Other interactions of Pdx1

  • 5. At earlier stages, only a dorsal bud rudiment forms transiently and expresses the transcription factors Ipf1 and Hlxb9 but lacks the key transcription factor involved in the acquisition of a pancreatic fate, Ptf1a, as well as all endocrine precursor cells [28].
  • Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner [29].
  • These findings demonstrate that Pdx1 expression is essential for integrating GLP-1R-dependent signals regulating alpha-cell glucagon secretion and for the growth, differentiated function, and survival of islet beta-cells [30].
  • In normal embryos, HNF-6 was detected in the endoderm prior to the expression of Pdx-1 [24].
  • Endodermal expression of Nkx6 genes depends differentially on Pdx1 [31].

Analytical, diagnostic and therapeutic context of Pdx1

  • Its migration is identical to that of in vitro translated STF1 in electrophoretic mobility-shift assays; it is specifically recognized by anti-STF1 antibodies and has an apparent molecular mass of 46 kDa [32].
  • To determine which beta-cell promoters are bound by Pdx1 in vivo, we performed chromatin immunoprecipitation assays using Pdx1 antiserum and chromatin from beta-TC3 cells and Pdx1-transfected NIH3T3 cells and subsequently quantitated co-immunoprecipitated promoters using real-time PCR [33].
  • We compared these in vivo findings to parallel immunoprecipitations in which Pdx1 was allowed to bind to promoter fragments in in vitro reactions [33].
  • Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding [33].
  • The failure of pdx-1 to inhibit endogenous proglucagon gene expression was not attributable to defects in Pdx-1 nuclear translocation or DNA binding as demonstrated using Western blotting and EMSA analyses [34].


  1. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Kim, S.K., Selleri, L., Lee, J.S., Zhang, A.Y., Gu, X., Jacobs, Y., Cleary, M.L. Nat. Genet. (2002) [Pubmed]
  2. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Kojima, H., Fujimiya, M., Matsumura, K., Younan, P., Imaeda, H., Maeda, M., Chan, L. Nat. Med. (2003) [Pubmed]
  3. Pdx1 restores beta cell function in Irs2 knockout mice. Kushner, J.A., Ye, J., Schubert, M., Burks, D.J., Dow, M.A., Flint, C.L., Dutta, S., Wright, C.V., Montminy, M.R., White, M.F. J. Clin. Invest. (2002) [Pubmed]
  4. Adenovirus Transduction is Required for the Correction of Diabetes Using Pdx-1 or Neurogenin-3 in the Liver. Wang, A.Y., Ehrhardt, A., Xu, H., Kay, M.A. Mol. Ther. (2007) [Pubmed]
  5. Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis. Ashraf, A., Abdullatif, H., Hardin, W., Moates, J.M. Pediatric diabetes. (2005) [Pubmed]
  6. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nakae, J., Biggs, W.H., Kitamura, T., Cavenee, W.K., Wright, C.V., Arden, K.C., Accili, D. Nat. Genet. (2002) [Pubmed]
  7. Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. St-Onge, L., Sosa-Pineda, B., Chowdhury, K., Mansouri, A., Gruss, P. Nature (1997) [Pubmed]
  8. Insulin-promoter-factor 1 is required for pancreas development in mice. Jonsson, J., Carlsson, L., Edlund, T., Edlund, H. Nature (1994) [Pubmed]
  9. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Fujitani, Y., Fujitani, S., Boyer, D.F., Gannon, M., Kawaguchi, Y., Ray, M., Shiota, M., Stein, R.W., Magnuson, M.A., Wright, C.V. Genes Dev. (2006) [Pubmed]
  10. Development of diabetes mellitus in aging transgenic mice following suppression of pancreatic homeoprotein IDX-1. Thomas, M.K., Devon, O.N., Lee, J.H., Peter, A., Schlosser, D.A., Tenser, M.S., Habener, J.F. J. Clin. Invest. (2001) [Pubmed]
  11. beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Ahlgren, U., Jonsson, J., Jonsson, L., Simu, K., Edlund, H. Genes Dev. (1998) [Pubmed]
  12. Mapping of the insulin promoter factor 1 gene (Ipf1) to distal mouse chromosome 5. Fiedorek, F.T., Kay, E.S. Genomics (1995) [Pubmed]
  13. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs, W.H., Wright, C.V., White, M.F., Arden, K.C., Accili, D. J. Clin. Invest. (2002) [Pubmed]
  14. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Martín, M., Gallego-Llamas, J., Ribes, V., Kedinger, M., Niederreither, K., Chambon, P., Dollé, P., Gradwohl, G. Dev. Biol. (2005) [Pubmed]
  15. The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix factor binding site. Serup, P., Petersen, H.V., Pedersen, E.E., Edlund, H., Leonard, J., Petersen, J.S., Larsson, L.I., Madsen, O.D. Biochem. J. (1995) [Pubmed]
  16. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. Shih, D.Q., Heimesaat, M., Kuwajima, S., Stein, R., Wright, C.V., Stoffel, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas. Apelqvist, A., Ahlgren, U., Edlund, H. Curr. Biol. (1997) [Pubmed]
  18. Effects of rosiglitazone and metformin on pancreatic beta cell gene expression. Richardson, H., Campbell, S.C., Smith, S.A., Macfarlane, W.M. Diabetologia (2006) [Pubmed]
  19. Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Micallef, S.J., Janes, M.E., Knezevic, K., Davis, R.P., Elefanty, A.G., Stanley, E.G. Diabetes (2005) [Pubmed]
  20. Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2. Cissell, M.A., Zhao, L., Sussel, L., Henderson, E., Stein, R. J. Biol. Chem. (2003) [Pubmed]
  21. Pancreatic-duodenal homeobox 1 -role in gastric endocrine patterning. Larsson, L.I., Madsen, O.D., Serup, P., Jonsson, J., Edlund, H. Mech. Dev. (1996) [Pubmed]
  22. Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy. Keller, D.M., McWeeney, S., Arsenlis, A., Drouin, J., Wright, C.V., Wang, H., Wollheim, C.B., White, P., Kaestner, K.H., Goodman, R.H. J. Biol. Chem. (2007) [Pubmed]
  23. Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum. Heller, R.S., Stoffers, D.A., Hussain, M.A., Miller, C.P., Habener, J.F. Gastroenterology (1998) [Pubmed]
  24. The Onecut transcription factor HNF-6 (OC-1) is required for timely specification of the pancreas and acts upstream of Pdx-1 in the specification cascade. Jacquemin, P., Lemaigre, F.P., Rousseau, G.G. Dev. Biol. (2003) [Pubmed]
  25. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha. Song, S.Y., Gannon, M., Washington, M.K., Scoggins, C.R., Meszoely, I.M., Goldenring, J.R., Marino, C.R., Sandgren, E.P., Coffey, R.J., Wright, C.V., Leach, S.D. Gastroenterology (1999) [Pubmed]
  26. Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression. Nomura, S., Settle, S.H., Leys, C.M., Means, A.L., Peek, R.M., Leach, S.D., Wright, C.V., Coffey, R.J., Goldenring, J.R. Gastroenterology (2005) [Pubmed]
  27. Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. Chen, L., Yan, H.X., Chen, J., Yang, W., Liu, Q., Zhai, B., Cao, H.F., Liu, S.Q., Wu, M.C., Wang, H.Y. Endocrinology (2007) [Pubmed]
  28. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Haumaitre, C., Barbacci, E., Jenny, M., Ott, M.O., Gradwohl, G., Cereghini, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner. Suzuki, R., Tobe, K., Terauchi, Y., Komeda, K., Kubota, N., Eto, K., Yamauchi, T., Azuma, K., Kaneto, H., Taguchi, T., Koga, T., German, M.S., Watada, H., Kawamori, R., Wright, C.V., Kajimoto, Y., Kimura, S., Nagai, R., Kadowaki, T. J. Biol. Chem. (2003) [Pubmed]
  30. beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Li, Y., Cao, X., Li, L.X., Brubaker, P.L., Edlund, H., Drucker, D.J. Diabetes (2005) [Pubmed]
  31. Endodermal expression of Nkx6 genes depends differentially on Pdx1. Pedersen, J.K., Nelson, S.B., Jorgensen, M.C., Henseleit, K.D., Fujitani, Y., Wright, C.V., Sander, M., Serup, P. Dev. Biol. (2005) [Pubmed]
  32. Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes. Petersen, H.V., Serup, P., Leonard, J., Michelsen, B.K., Madsen, O.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  33. Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding. Chakrabarti, S.K., James, J.C., Mirmira, R.G. J. Biol. Chem. (2002) [Pubmed]
  34. Pdx-1 is not sufficient for repression of proglucagon gene transcription in islet or enteroendocrine cells. Flock, G., Cao, X., Drucker, D.J. Endocrinology (2005) [Pubmed]
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