Genomes and Genes
Gene Symbol: Pdx1
Description: pancreatic and duodenal homeobox 1
Alias: IDX-1, IPF-1, Ipf1, Mody4, STF-1, pdx-1, pancreas/duodenum homeobox protein 1, insulin promoter factor 1, homeodomain transcription factor, islet/duodenum homeobox 1, pancreatic and duodenal homeobox gene 1, somatostatin-transactivating factor 1
Publications104 found, 100 shown here
- Gerrish K, Gannon M, Shih D, Henderson E, Stoffel M, Wright C, et al. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. J Biol Chem. 2000;275:3485-92 pubmed..Together, these results suggest that the conserved sequences represented by areas I and II define the binding sites for factors such as HNF3beta, which control islet beta cell-selective expression of the pdx-1 gene. ..
- 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 U S A. 2000;97:1607-11 pubmed..Recent genetic studies have identified a network of transcription factors, including Pdx1, Isl1, Pax4, Pax6, NeuroD, Nkx2...
- Jensen J, Heller R, Funder Nielsen T, Pedersen E, Lindsell C, Weinmaster G, et al. Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes. 2000;49:163-76 pubmed..beta-cells have been suggested to arise late, directly from the GLUT2- and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage...
- Campbell S, Macfarlane W. Regulation of the pdx1 gene promoter in pancreatic beta-cells. Biochem Biophys Res Commun. 2002;299:277-84 pubmedIn the adult pancreas the expression of the transcription factor PDX1 is mainly restricted to the beta-cells of the islets of Langerhans...
- Alanentalo T, Chatonnet F, Karlen M, Sulniute R, Ericson J, Andersson E, et al. Cloning and analysis of Nkx6.3 during CNS and gastrointestinal development. Gene Expr Patterns. 2006;6:162-70 pubmed..2 both in the CNS and in the gut. Transient Nkx6.2 expression was also detected in the developing pancreas. However, analysis of Nkx6.2(-/-) mice did not display any obvious aberrations of pancreatic or stomach development. ..
- Ahlgren U, Pfaff S, Jessell T, Edlund T, Edlund H. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature. 1997;385:257-60 pubmed
- Kawaguchi Y, Cooper B, Gannon M, Ray M, Macdonald R, Wright C. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet. 2002;32:128-34 pubmed..Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null ..
- Bort R, Martinez Barbera J, Beddington R, Zaret K. Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development. 2004;131:797-806 pubmed..Other endodermal transcription factors may also function morphogenetically rather than by directly regulating tissue-specific programs. ..
- Iype T, Francis J, Garmey J, Schisler J, Nesher R, Weir G, et al. Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. J Biol Chem. 2005;280:16798-807 pubmed..This complex leads to enhancement of elongation by the basal transcriptional machinery. ..
- Li S, Francisco A, Munroe R, Schimenti J, Long Q. SEL1L deficiency impairs growth and differentiation of pancreatic epithelial cells. BMC Dev Biol. 2010;10:19 pubmed publisher..Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development. ..
- Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, et al. Pdx1 maintains ? cell identity and function by repressing an ? cell program. Cell Metab. 2014;19:259-71 pubmed publisherb>Pdx1 is a homeobox-containing transcription factor that plays a key role in pancreatic development and adult ? cell function. In this study, we traced the fate of adult ? cells after Pdx1 deletion...
- Suzuki A, Nakauchi H, Taniguchi H. Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci U S A. 2003;100:5034-9 pubmed..Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus. ..
- Norgaard G, Jensen J, Jensen J. FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development. Dev Biol. 2003;264:323-38 pubmed..In the pancreas, mesenchymal FGF10 is required to maintain the Pdx1-expressing epithelial progenitor cell population, and in the absence of FGF10 signaling, these cells fail to ..
- Yoshitomi H, Zaret K. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development. 2004;131:807-17 pubmed..that the initial induction of dorsal endoderm cells positive for the pancreatic and duodenal transcription factor Pdx1 does not require aorta or endothelial cell interactions, but dorsal pancreatic bud emergence and the maintenance of ..
- Wicksteed B, Brissova M, Yan W, Opland D, Plank J, Reinert R, et al. Conditional gene targeting in mouse pancreatic ß-Cells: analysis of ectopic Cre transgene expression in the brain. Diabetes. 2010;59:3090-8 pubmed publisher..Transgenic Cre lines driven by Ins1, Ins2, and Pdx1 promoters were bred to R26R reporter strains...
- Yang Y, Thorel F, Boyer D, Herrera P, Wright C. Context-specific ?- to-?-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011;25:1680-5 pubmed publisher..We enforced Pdx1 expression from the Neurogenin-3-expressing endocrine commitment point onward and found during the embryonic period ..
- Akinci E, Banga A, Greder L, Dutton J, Slack J. Reprogramming of pancreatic exocrine cells towards a beta (?) cell character using Pdx1, Ngn3 and MafA. Biochem J. 2012;442:539-50 pubmed publisherb>Pdx1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3) and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A) have been reported to bring about the transdifferentiation of pancreatic exocrine cells to beta (?) ..
- Bhushan A, Itoh N, Kato S, Thiery J, Czernichow P, Bellusci S, et al. Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development. 2001;128:5109-17 pubmed..reduction in the proliferation of the epithelial progenitor cells marked by the production of the homeobox protein PDX1. Furthermore, FGF10 restores the population of PDX1-positive cells in organ cultures derived from Fgf10(-/-) ..
- Fujitani Y, Fujitani S, Boyer D, Gannon M, Kawaguchi Y, Ray M, et al. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev. 2006;20:253-66 pubmedb>Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas development and mature beta-cell function...
- Seymour P, Freude K, Dubois C, Shih H, Patel N, Sander M. A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation. Dev Biol. 2008;323:19-30 pubmed publisher..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD. ..
- Schwitzgebel V, Scheel D, Conners J, Kalamaras J, Lee J, Anderson D, et al. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development. 2000;127:3533-42 pubmed..5. Although not detected in cells expressing islet hormones or the islet transcription factors Isl1, Brn4, Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation factors Nkx6.1 and Nkx2...
- Gannon M, Gamer L, Wright C. Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. Dev Biol. 2001;238:185-201 pubmedb>pdx1 (pancreatic and duodenal homeobox gene-1), which is expressed broadly in the embryonic pancreas and, later, in a more restricted manner in the mature beta cells in the islets of Langerhans, is essential both for organ formation and ..
- Kushner J, Ye J, Schubert M, Burks D, Dow M, Flint C, et al. Pdx1 restores beta cell function in Irs2 knockout mice. J Clin Invest. 2002;109:1193-201 pubmedThe homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of beta cells...
- Wang S, Yan J, Anderson D, Xu Y, Kanal M, Cao Z, et al. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev Biol. 2010;339:26-37 pubmed publisher..The control of Neurog3+ cell number and the Neurog3 threshold-dependent endocrine differentiation mechanism combine to select a specific proportion of pancreatic progenitor cells to adopt the islet cell fate. ..
- Moens C, Selleri L. Hox cofactors in vertebrate development. Dev Biol. 2006;291:193-206 pubmed
- Fukuda A, Kawaguchi Y, Furuyama K, Kodama S, Horiguchi M, Kuhara T, et al. Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice. Diabetes. 2008;57:2421-31 pubmed publisher..Interestingly, Pdx1 expression was decreased in early pancreatic progenitors but elevated to normal level at the mid-to-late stages of ..
- Haumaitre C, Barbacci E, Jenny M, Ott M, Gradwohl G, Cereghini S. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Proc Natl Acad Sci U S A. 2005;102:1490-5 pubmed..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 ..
- Pedersen J, Nelson S, Jorgensen M, Henseleit K, Fujitani Y, Wright C, et al. Endodermal expression of Nkx6 genes depends differentially on Pdx1. Dev Biol. 2005;288:487-501 pubmed..In mice, expression of Nkx6.1 is restricted to the pancreatic epithelium. In both mice and chicken, Nkx6.2 and Pdx1 are expressed in very similar domains, identifying Nkx6.2 as a novel marker of pancreas endoderm...
- Apelqvist A, Ahlgren U, Edlund H. Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas. Curr Biol. 1997;7:801-4 pubmed..the exception of the pancreatic bud endoderm, which instead expresses high levels of the homeodomain protein Ipf1/Pdx1 (insulin promoter factor 1/pancreatic and duodenal homeobox 1), an essential regulator of early pancreatic ..
- Vincent M, Guz Y, Rozenberg M, Webb G, Furuta M, Steiner D, et al. Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis. Endocrinology. 2003;144:4061-9 pubmed..These results indicate that hormones processed by PC2 affected processes that regulate islet cell differentiation and maturation in embryos and adults. ..
- Papadopoulou S, Edlund H. Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. Diabetes. 2005;54:2844-51 pubmed..Collectively, our data provide evidence that Wnt signaling is required for pancreatic growth but not adult beta-cell function. ..
- Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed..However, Pdx1, Nkx6.1, and GLUT2 were selectively lost in these insulin-deficient cells between E15.5 and E18.5...
- Svensson P, Williams C, Lundeberg J, Ryden P, Bergqvist I, Edlund H. Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic progenitor cells. BMC Dev Biol. 2007;7:129 pubmedThe homeodomain transcription factor IPF1/PDX1 exerts a dual role in the pancreas; Ipf1/Pdx1 global null mutants fail to develop a pancreas whereas conditional inactivation of Ipf1/Pdx1 in beta-cells leads to impaired beta-cell function ..
- Boucher M, Simoneau M, Edlund H. The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. Endocrinology. 2009;150:87-97 pubmed publisher..Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased ..
- Pulkkinen M, Spencer Dene B, Dickson C, Otonkoski T. The IIIb isoform of fibroblast growth factor receptor 2 is required for proper growth and branching of pancreatic ductal epithelium but not for differentiation of exocrine or endocrine cells. Mech Dev. 2003;120:167-75 pubmed..Our results thus suggest that Fgfr2b-mediated signaling plays a major role in pancreatic ductal proliferation and branching morphogenesis, but has little effect on endocrine and exocrine differentiation. ..
- Jonsson J, Ahlgren U, Edlund T, Edlund H. IPF1, a homeodomain protein with a dual function in pancreas development. Int J Dev Biol. 1995;39:789-98 pubmedInsulin promoter factor 1 (IPF1), is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in beta-cells, and which binds to, and transactivates, the insulin promoter via the P1 element...
- Harrison K, Thaler J, Pfaff S, Gu H, Kehrl J. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet. 1999;23:71-5 pubmed..Gene targeting experiments have revealed critical roles for Pdx1, Isl1, Pax4, Pax6 and Nkx2-2 (refs 3,4,5,6,7, 8,9,10)...
- Song S, Gannon M, Washington M, Scoggins C, Meszoely I, Goldenring J, et al. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha. Gastroenterology. 1999;117:1416-26 pubmed..During pancreatic development, differentiated cell types arise from ductal progenitor cells expressing the Pdx1 homeodomain transcription factor...
- Johnson J, Ahmed N, Luciani D, Han Z, Tran H, Fujita J, et al. Increased islet apoptosis in Pdx1+/- mice. J Clin Invest. 2003;111:1147-60 pubmedMice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas...
- Liu A, Desai B, Stoffers D. Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. Mol Cell Biol. 2004;24:4372-83 pubmed..The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. ..
- Kulkarni R, Jhala U, Winnay J, Krajewski S, Montminy M, Kahn C. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest. 2004;114:828-36 pubmed..This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. ..
- Oster A, Jensen J, Edlund H, Larsson L. Homeobox gene product Nkx 6.1 immunoreactivity in nuclei of endocrine cells of rat and mouse stomach. J Histochem Cytochem. 1998;46:717-21 pubmed..1-positive nuclei. Our data show that Pdx-1 is needed for Nkx 6.1 expression and suggest a role for Nkx 6.1 in the maturation of gastrin- and serotonin-positive precursor cells...
- Gerrish K, Van Velkinburgh J, Stein R. Conserved transcriptional regulatory domains of the pdx-1 gene. Mol Endocrinol. 2004;18:533-48 pubmed..Our data suggests that pdx-1 transcription is also regulated by factors acting upon conserved area IV sequences. ..
- Wang J, Elghazi L, Parker S, Kizilocak H, Asano M, Sussel L, et al. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol. 2004;266:178-89 pubmed..essential for appropriate initiation of beta-cell differentiation because loss of Pax4 prevents the expression of Pdx1, HB9 and insulin in beta-cell precursors...
- Lee C, Sund N, Behr R, Herrera P, Kaestner K. Foxa2 is required for the differentiation of pancreatic alpha-cells. Dev Biol. 2005;278:484-95 pubmed..By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. ..
- Seymour P, Freude K, Tran M, Mayes E, Jensen J, Kist R, et al. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A. 2007;104:1865-70 pubmed..In the developing pancreas, SOX9 expression is restricted to a mitotically active, Notch-responsive subset of PDX1(+) pluripotent progenitors and is absent from committed endocrine precursors or differentiated cells...
- Nir T, Melton D, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553-61 pubmed..These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs. ..
- Bernardo A, Cho C, Mason S, Docherty H, Pedersen R, Vallier L, et al. Biphasic induction of Pdx1 in mouse and human embryonic stem cells can mimic development of pancreatic beta-cells. Stem Cells. 2009;27:341-51 pubmed publisher..a detailed understanding of how the transcription factor cascade initiated by the homeodomain transcription factor Pdx1 culminates in pancreatic beta-cell development...
- Spence J, Lange A, Lin S, Kaestner K, Lowy A, Kim I, et al. Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. Dev Cell. 2009;17:62-74 pubmed publisher..These pancreatobiliary progenitor cells coexpress the transcription factors PDX1 and SOX17 at E8...
- Maestro M, Boj S, Luco R, Pierreux C, Cabedo J, Servitja J, et al. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet. 2003;12:3307-14 pubmed..These findings define a precursor cellular stage of the embryonic pancreas and place Hnf1beta in a genetic hierarchy that regulates the generation of pancreatic endocrine cells. ..
- CHAO C, Loomis Z, Lee J, Sussel L. Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev Biol. 2007;312:523-32 pubmed..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells. ..
- Xuan S, Borok M, Decker K, Battle M, Duncan S, Hale M, et al. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. J Clin Invest. 2012;122:3516-28 pubmed publisher..few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases...
- Holland A, Hale M, Kagami H, Hammer R, Macdonald R. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A. 2002;99:12236-41 pubmedTo investigate the role of the HOX-like homeoprotein PDX1 in the formation and maintenance of the pancreas, we have genetically engineered mice so that the only source of PDX1 is a transgene that can be controlled by the application of ..
- Hart A, Papadopoulou S, Edlund H. Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells. Dev Dyn. 2003;228:185-93 pubmed..Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway. ..
- Heller R, Stoffers D, Liu A, Schedl A, Crenshaw E, Madsen O, et al. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol. 2004;268:123-34 pubmed..2 cells. The pancreatic phenotype of the pax6 mutants can be rescued with a YAC clone containing the human Pax6 gene. ..
- Ahnfelt Rønne J, Jørgensen M, Hald J, Madsen O, Serup P, Hecksher Sørensen J. An improved method for three-dimensional reconstruction of protein expression patterns in intact mouse and chicken embryos and organs. J Histochem Cytochem. 2007;55:925-30 pubmed..This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. ..
- Ioannou M, Serafimidis I, Arnés L, Sussel L, Singh S, Vasiliou V, et al. ALDH1B1 is a potential stem/progenitor marker for multiple pancreas progenitor pools. Dev Biol. 2013;374:153-63 pubmed publisher..5 dpc) in a Pdx1 dependent manner...
- Offield M, Jetton T, Labosky P, Ray M, Stein R, Magnuson M, et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996;122:983-95 pubmed..These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors. ..
- Kanai Azuma M, Kanai Y, Gad J, Tajima Y, Taya C, Kurohmaru M, et al. Depletion of definitive gut endoderm in Sox17-null mutant mice. Development. 2002;129:2367-79 pubmed..Our findings indicate an important role of Sox17 in endoderm development in the mouse, highlighting the idea that the molecular mechanism for endoderm formation is likely to be conserved among vertebrates. ..
- Ber I, Shternhall K, Perl S, Ohanuna Z, Goldberg I, Barshack I, et al. Functional, persistent, and extended liver to pancreas transdifferentiation. J Biol Chem. 2003;278:31950-7 pubmed..Transconversion of liver to pancreas may serve as a novel approach for generating endocrine-pancreatic tissue that can replace malfunctioning beta-cells in diabetics. ..
- Jensen J. Gene regulatory factors in pancreatic development. Dev Dyn. 2004;229:176-200 pubmed..Developmental Dynamics 229:176-200, 2004. ..
- Hecksher Sørensen J, Watson R, Lettice L, Serup P, Eley L, De Angelis C, et al. The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2. Development. 2004;131:4665-75 pubmed..We conclude that the SMP is an organiser responsible for the leftward growth of the spleno-pancreatic region and that Bapx1 regulates SMP functions required for pancreatic laterality. ..
- Stanger B, Datar R, Murtaugh L, Melton D. Direct regulation of intestinal fate by Notch. Proc Natl Acad Sci U S A. 2005;102:12443-8 pubmed..In the embryo, Notch activation perturbs morphogenesis, possibly through effects on stem or progenitor cells. ..
- Miyatsuka T, Kaneto H, Shiraiwa T, Matsuoka T, Yamamoto K, Kato K, et al. Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation. Genes Dev. 2006;20:1435-40 pubmed..These results provide a mechanism of pancreatic metaplasia by which persistent PDX-1 expression cell-autonomously induces acinar-to-ductal transition through Stat3 activation. ..
- Gerrish K, Cissell M, Stein R. The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem. 2001;276:47775-84 pubmed
- Kim S, Selleri L, Lee J, Zhang A, Gu X, Jacobs Y, et al. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Nat Genet. 2002;30:430-5 pubmed..In vitro studies have shown that Pbx1 regulates the activity of Ipf1 (also known as Pdx1), a ParaHox homeodomain transcription factor required for the development and function of the pancreas in mice and ..
- Thomas I, Saini N, Adhikari A, Lee J, Kasa Vubu J, Vazquez D, et al. Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation. Pediatr Diabetes. 2009;10:492-6 pubmed publisher..This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human. ..
- Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev. 1998;12:1763-8 pubmedTo study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells...
- Chiang M, Melton D. Single-cell transcript analysis of pancreas development. Dev Cell. 2003;4:383-93 pubmed..This form of single-cell transcriptional analysis can be applied to any developmental process or tissue to characterize distinct cell types. ..
- Matsuoka T, Zhao L, Artner I, Jarrett H, Friedman D, Means A, et al. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol. 2003;23:6049-62 pubmed..Because MafA, MafB, and c-Maf were each capable of specifically binding to and activating insulin C1 element-mediated expression, our results suggest that all of these factors play a role in islet beta-cell function. ..
- Holland A, Gonez L, Naselli G, Macdonald R, Harrison L. Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas. Diabetes. 2005;54:2586-95 pubmedThe homeodomain transcription factor Pdx1 is essential for pancreas development...
- Sachdeva M, Claiborn K, Khoo C, Yang J, Groff D, Mirmira R, et al. Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress. Proc Natl Acad Sci U S A. 2009;106:19090-5 pubmed publisher..pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes...
- Schaffer A, Freude K, Nelson S, Sander M. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell. 2010;18:1022-9 pubmed publisher..Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development. ..
- Du A, McCracken K, Walp E, Terry N, Klein T, Han A, et al. Arx is required for normal enteroendocrine cell development in mice and humans. Dev Biol. 2012;365:175-88 pubmed publisher..Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations. ..
- Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, et al. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development. 2000;127:5533-40 pubmed..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation. ..
- Melloul D, Marshak S, Cerasi E. Regulation of pdx-1 gene expression. Diabetes. 2002;51 Suppl 3:S320-5 pubmed..We postulate that disruption of pdx-1 cis-acting regulatory sequences and/or mutations or functional impairment of transcription factors controlling the expression of the gene can lead to diabetes. ..
- Esni F, Ghosh B, Biankin A, Lin J, Albert M, Yu X, et al. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development. 2004;131:4213-24 pubmed..These results define a normal inhibitory role for Notch in the regulation of exocrine pancreatic differentiation. ..
- Doyle M, Loomis Z, Sussel L. Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number of beta-cells in the pancreatic islet. Development. 2007;134:515-23 pubmed..2 through its TN domain. These studies suggest that Nkx2.2 functions predominantly as a transcriptional repressor during specification of endocrine cell types in the pancreas. ..
- Wang S, Zhang J, Zhao A, Hipkens S, Magnuson M, Gu G. Loss of Myt1 function partially compromises endocrine islet cell differentiation and pancreatic physiological function in the mouse. Mech Dev. 2007;124:898-910 pubmed..The consequences of Myt1 inactivation in the developing pancreas could be masked by activation of its paralogs, Myt1l and Myt3. These findings suggest Myt1 is involved in proper endocrine differentiation and function. ..
- Hart A, Baeza N, Apelqvist A, Edlund H. Attenuation of FGF signalling in mouse beta-cells leads to diabetes. Nature. 2000;408:864-8 pubmed..These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human...
- Chakrabarti S, James J, Mirmira R. Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding. J Biol Chem. 2002;277:13286-93 pubmedThe transcription factor Pdx1 is expressed in the pancreatic beta-cell, where it is believed to regulate several beta-cell-specific genes...
- Van Velkinburgh J, Samaras S, Gerrish K, Artner I, Stein R. Interactions between areas I and II direct pdx-1 expression specifically to islet cell types of the mature and developing pancreas. J Biol Chem. 2005;280:38438-44 pubmed..These results suggest that Area II is a central pdx-1 control region, whose islet cell activity is uniquely modified by Area I regulatory factors. ..
- Burlison J, Long Q, Fujitani Y, Wright C, Magnuson M. Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells. Dev Biol. 2008;316:74-86 pubmed publisher..Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification. ..
- Kim S, Rane S. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors. Development. 2011;138:1903-12 pubmed publisher..Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1(+) pancreatic progenitor cells. Expression of activated Cdk4(R24C) kinase leads to increased Nkx2.2(+) and Nkx6...
- Mastracci T, Wilcox C, Arnés L, Panea C, Golden J, MAY C, et al. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Dev Biol. 2011;359:1-11 pubmed publisher..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells. ..
- Krapp A, Knöfler M, Ledermann B, Burki K, Berney C, Zoerkler N, 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. 1998;12:3752-63 pubmed
- Decker K, Goldman D, Grasch C, Sussel L. Gata6 is an important regulator of mouse pancreas development. Dev Biol. 2006;298:415-29 pubmed..Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests that Gata6 is an important regulator of pancreas specification. ..
- Kim B, Miletich I, Mao J, McMahon A, Sharpe P, Shivdasani R. Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. Development. 2007;134:3603-13 pubmed..These observations place Barx1 proximally within a Wt1 pathway of spleen development and reveal how a homeotic regulator employs different molecular mechanisms to mold neighboring organs. ..