3,488
Views
51
CrossRef citations to date
0
Altmetric
Review

Transcription factor regulation of pancreatic organogenesis, differentiation and maturation

, &
Pages 13-34 | Received 22 Dec 2014, Accepted 17 Jul 2015, Published online: 22 Mar 2016

References

  • Slack JM. Developmental biology of the pancreas. Development 1995; 121:1569-80; PMID:7600975
  • Jones PM, Persaud SJ. Textbook of diabetes. 4th ed. UK: Blackwell Publishing Ltd; c2010. Chapter 6, Islet function and insulin secretion; 87-101
  • American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33:S62-9; PMID:20042775; http://dx.doi.org/10.2337/dc10-S062
  • Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New Engl J Med 2000; 343:230-8; PMID:10911004; http://dx.doi.org/10.1056/NEJM200007273430401
  • Larsen JL, Colling CW, Ratanasuwan T, Burkman TW, Lynch TG, Erickson JM, Lyden ER, Lane JT, Mack-Shipman LR. Pancreas transplantation improves vascular disease in patients with type 1 diabetes. Diabetes Care 2004; 27:1706-11; PMID:15220250; http://dx.doi.org/10.2337/diacare.27.7.1706
  • D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006; 24:1392-401; PMID:17053790; http://dx.doi.org/10.1038/nbt1259
  • Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, Majumdar AS. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 2007; 25:1940-53; PMID:17510217; http://dx.doi.org/10.1634/stemcells.2006-0761
  • Banga A, Akinci E, Greder LV, Dutton JR, Slack JM. In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci USA 2012; 109:15336-41; http://dx.doi.org/10.1073/pnas.1201701109
  • Akinci E, Banga A, Greder LV, Dutton JR, Slack JM. Reprogramming of pancreatic exocrine cells towards a β cell character using Pdx1, Ngn3 and MafA. Biochem J 2012; 442:539-50; PMID:22150363; http://dx.doi.org/10.1042/BJ20111678
  • Lima MJ, Docherty HM, Chen Y, Docherty K. Efficient differentiation of AR42J cells towards insulin-producing cells using pancreatic transcription factors in combination with growth factors. Mol Cell Endocrinol 2012; 358:69-80; PMID:22429991; http://dx.doi.org/10.1016/j.mce.2012.02.024
  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 2008; 455:627-32; PMID:18754011; http://dx.doi.org/10.1038/nature07314
  • Thorel F, Nepote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL. Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature 2010; 464:1149-54; PMID:20364121; http://dx.doi.org/10.1038/nature08894
  • Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nature Genetics 2012; 44:406-12; PMID:22406641; http://dx.doi.org/10.1038/ng.2215
  • Mfopou JK, Chen B, Sui L, Sermon K, Bouwens L. Recent advances and prospects in the differentiation of pancreatic cells from human embryonic stem cells. Diabetes 2010; 59:2094-101; PMID:20805383; http://dx.doi.org/10.2337/db10-0439
  • Guney MA, Gannon M. Pancreas cell fate. Birth Defects Res C Embryo Today 2009; 87:232-48; PMID:19750517; http://dx.doi.org/10.1002/bdrc.20156
  • Pictet RL, Clark WR, Williams RH, Rutter WJ. An ultrastructural analysis of the developing embryonic pancreas. Dev Biol 1972; 29:436-67; PMID:4570759; http://dx.doi.org/10.1016/0012-1606(72)90083-8
  • Spooner BS, Walther BT, Rutter WJ. The development of the dorsal and ventral mammalian pancreas in vivo and in vitro. J Cell Biol 1970; 47:235-46; PMID:5513553; http://dx.doi.org/10.1083/jcb.47.1.235
  • Pictet RL, Rutter WJ. Handbook of physiology. Baltimore: Williams and Wilkins; c1972. Section 7, Endocrinology, endocrine pancreas; 25-66
  • Lin CL, Vuguin PM. Determinants of pancreatic islet development in mice and men: a focus on the role of transcription factors. Horm Res Paediatr 2012; 77:205-13; PMID:22487552; http://dx.doi.org/10.1159/000337219
  • Oliver-Krasinski JM, Stoffers DA. On the origin of the β cell. Genes Dev 2008; 22:1998-2021; PMID:18676806; http://dx.doi.org/10.1101/gad.1670808
  • Kim SK, Hebrok M. Intercellular signals regulating pancreas development and function. Genes Dev 2001; 15:111-27; PMID:11157769; http://dx.doi.org/10.1101/gad.859401
  • Prasadan K, Daume E, Preuett B, Spilde T, Bhatia A, Kobayashi H, Hembree M, Manna P, Gittes GK. Glucagon is required for early insulin-positive differentiation in the developing mouse pancreas. Diabetes 2002; 51:3229-36; PMID:12401714; http://dx.doi.org/10.2337/diabetes.51.11.3229
  • Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development 2000; 127:2317-22; PMID:10804174
  • Kesavan G, Sand FW, Greiner TU, Johansson JK, Kobberup S, Wu X, Brakebusch C, Semb H. Cdc42-mediated tubulogenesis controls cell specification. Cell 2009; 139:791-801; PMID:19914171; http://dx.doi.org/10.1016/j.cell.2009.08.049
  • Villasenor A, Chong DC, Henkemeyer M, Cleaver O. Epithelial dynamics of pancreatic branching morphogenesis. Development 2010; 137:4295-305; PMID:21098570; http://dx.doi.org/10.1242/dev.052993
  • Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 1997; 385:257-60; PMID:9000074; http://dx.doi.org/10.1038/385257a0
  • Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 1996; 122:983-95; PMID:8631275
  • Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002; 32:128-34; PMID:12185368; http://dx.doi.org/10.1038/ng959
  • Burlison JS, Long Q, Fujitani Y, Wright CV, Magnuson MA. Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells. Dev Biol 2008; 316:74-86; PMID:18294628; http://dx.doi.org/10.1016/j.ydbio.2008.01.011
  • Chiang MK, Melton DA. Single-cell transcript analysis of pancreas development. Deve Cell 2003; 4:383-93; PMID:12636919; http://dx.doi.org/10.1016/S1534-5807(03)00035-2
  • Jorgensen MC, Ahnfelt-Ronne J, Hald J, Madsen OD, Serup P, Hecksher-Sorensen J. An illustrated review of early pancreas development in the mouse. Endocr Rev 2007; 28:685-705; PMID:17881611; http://dx.doi.org/10.1210/er.2007-0016
  • Gittes GK. Developmental biology of the pancreas: a comprehensive review. Dev Biol 2009; 326:4-35; PMID:19013144; http://dx.doi.org/10.1016/j.ydbio.2008.10.024
  • Zhou Q, Law AC, Rajagopal J, Anderson WJ, Gray PA, Melton DA. A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell 2007; 13:103-14; PMID:17609113; http://dx.doi.org/10.1016/j.devcel.2007.06.001
  • Stanger BZ, Tanaka AJ, Melton DA. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 2007; 445:886-91; PMID:17259975; http://dx.doi.org/10.1038/nature05537
  • Rieck S, Bankaitis ED, Wright CV. Lineage determinants in early endocrine development. Semin Cell Dev Biol 2012; 23:673-84; PMID:22728667; http://dx.doi.org/10.1016/j.semcdb.2012.06.005
  • Ben-Othman N, Courtney M, Vieira A, Pfeifer A, Druelle N, Gjernes E, Faurite B, Avolio F, Collombat P. From pancreatic islet formation to β-cell regeneration. Diabetes Res Clin Prac 2013; 101:1-9; PMID:23380136; http://dx.doi.org/10.1016/j.diabres.2013.01.013
  • Cerf ME. Islet organogenesis, angiogenesis and innervation. Cell Biol Int 2011; 35:1065-78; PMID:21999312; http://dx.doi.org/10.1042/CBI20100780
  • Miller K, Kim A, Kilimnik G, Jo J, Moka U, Periwal V, Hara M. Islet formation during the neonatal development in mice. PloS One 2009; 4:e7739; PMID:19893748; http://dx.doi.org/10.1371/journal.pone.0007739
  • Villasenor A, Chong DC, Cleaver O. Biphasic Ngn3 expression in the developing pancreas. Dev Dynamics 2008; 237:3270-9; PMID:18924236; http://dx.doi.org/10.1002/dvdy.21740
  • Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 2004; 101:2924-9; http://dx.doi.org/10.1073/pnas.0308604100
  • Wierup N, Svensson H, Mulder H, Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regulatory Peptides 2002; 107:63-9; PMID:12137967; http://dx.doi.org/10.1016/S0167-0115(02)00067-8
  • Bouwens L, Rooman I. Regulation of pancreatic β-cell mass. Physiol Rev 2005; 85:1255-70; PMID:16183912; http://dx.doi.org/10.1152/physrev.00025.2004
  • Teta M, Rankin MM, Long SY, Stein GM, Kushner JA. Growth and regeneration of adult β cells does not involve specialized progenitors. Dev Cell 2007; 12:817-26; PMID:17488631; http://dx.doi.org/10.1016/j.devcel.2007.04.011
  • Rankin MM, Kushner JA. Adaptive β-cell proliferation is severely restricted with advanced age. Diabetes 2009; 58:1365-72; PMID:19265026; http://dx.doi.org/10.2337/db08-1198
  • Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004; 429:41-6; PMID:15129273; http://dx.doi.org/10.1038/nature02520
  • Finegood DT, Scaglia L, Bonner-Weir S. Dynamics of β-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 1995; 44:249-56; PMID:7883109; http://dx.doi.org/10.2337/diab.44.3.249
  • Teta M, Long SY, Wartschow LM, Rankin MM, Kushner JA. Very slow turnover of β-cells in aged adult mice. Diabetes 2005; 54:2557-67; PMID:16123343; http://dx.doi.org/10.2337/diabetes.54.9.2557
  • Beith JL, Alejandro EU, Johnson JD. Insulin stimulates primary β-cell proliferation via Raf-1 kinase. Endocrinol 2008; 149:2251-60; PMID:18202127; http://dx.doi.org/10.1210/en.2007-1557
  • Perl S, Kushner JA, Buchholz BA, Meeker AK, Stein GM, Hsieh M, Kirby M, Pechhold S, Liu EH, Harlan DM, et al. Significant human β-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating. J Clin Endocrinol Metab 2010; 95:E234-9; PMID:20660050; http://dx.doi.org/10.1210/jc.2010-0932
  • Weir GC, Laybutt DR, Kaneto H, Bonner-Weir S, Sharma A. Beta-cell adaptation and decompensation during the progression of diabetes. Diabetes 2001; 50:S154-9; PMID:11272180; http://dx.doi.org/10.2337/diabetes.50.2007.S154
  • Parsons JA, Brelje TC, Sorenson RL. Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinol 1992; 130:1459-66; PMID:1537300
  • Desai BM, Oliver-Krasinski J, De Leon DD, Farzad C, Hong N, Leach SD, Stoffers DA. Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration. J Clin Invest 2007; 117:971-7; PMID:17404620; http://dx.doi.org/10.1172/JCI29988
  • Jiang Z, Song J, Qi F, Xiao A, An X, Liu NA, Zhu Z, Zhang B, Lin S. Exdpf is a key regulator of exocrine pancreas development controlled by retinoic acid and ptf1a in zebrafish. PLoS Biol 2008; 6:e293; PMID:19067490; http://dx.doi.org/10.1371/journal.pbio.0060293
  • Collombat P, Hecksher-Sorensen J, Krull J, Berger J, Riedel D, Herrera PL, Serup P, Mansouri A. Embryonic endocrine pancreas and mature β cells acquire α and PP cell phenotypes upon Arx misexpression. J Clin Invest 2007; 117:961-70; PMID:17404619; http://dx.doi.org/10.1172/JCI29115
  • Murtaugh LC. Pancreas and β-cell development: from the actual to the possible. Development 2007; 134:427-38; PMID:17185316; http://dx.doi.org/10.1242/dev.02770
  • Li H, Arber S, Jessell TM, Edlund H. Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat Genet 1999; 23:67-70; PMID:10471501
  • Harrison KA, Thaler J, Pfaff SL, Gu H, Kehrl JH. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 1999; 23:71-5; PMID:10471502
  • Sherwood RI, Chen TY, Melton DA. Transcriptional dynamics of endodermal organ formation. Dev Dynam 2009; 238:29-42; PMID:19097184; http://dx.doi.org/10.1002/dvdy.21810
  • Li H, Edlund H. Persistent expression of Hlxb9 in the pancreatic epithelium impairs pancreatic development. Dev Biol 2001; 240:247-53; PMID:11784060; http://dx.doi.org/10.1006/dbio.2001.0440
  • Thor S, Ericson J, Brannstrom T, Edlund T. The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat. Neuron 1991; 7:881-9; PMID:1764243; http://dx.doi.org/10.1016/0896-6273(91)90334-V
  • Heddad Masson M, Poisson C, Guerardel A, Mamin A, Philippe J, Gosmain Y. Foxa1 and Foxa2 regulate α-cell differentiation, glucagon biosynthesis, and secretion. Endocrinol 2014; 155:3781-92; PMID:25057789; http://dx.doi.org/10.1210/en.2013-1843
  • Maestro MA, Cardalda C, Boj SF, Luco RF, Servitja JM, Ferrer J. Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, β-cell function and growth. Endocrine Dev 2007; 12:33-45; PMID:17923767; http://dx.doi.org/10.1159/000109603
  • Monaghan AP, Kaestner KH, Grau E, Schutz G. Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 α, β and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development 1993; 119:567-78; PMID:8187630
  • Ang SL, Wierda A, Wong D, Stevens KA, Cascio S, Rossant J, Zaret KS. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development 1993; 119:1301-15; PMID:8306889
  • Landry C, Clotman F, Hioki T, Oda H, Picard JJ, Lemaigre FP, Rousseau GG. 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 1997; 192:247-57; PMID:9441665; http://dx.doi.org/10.1006/dbio.1997.8757
  • Haumaitre C, Barbacci E, Jenny M, Ott MO, Gradwohl G, Cereghini S. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Proc Natl Acad Sci USA 2005; 102:1490-5
  • Solar M, Cardalda C, Houbracken I, Martin M, Maestro MA, De Medts N, Xu X, Grau V, Heimberg H, Bouwens L, et al. Pancreatic exocrine duct cells give rise to insulin-producing β cells during embryogenesis but not after birth. Dev Cell 2009; 17:849-60; PMID:20059954; http://dx.doi.org/10.1016/j.devcel.2009.11.003
  • Rausa F, Samadani U, Ye H, Lim L, Fletcher CF, Jenkins NA, Copeland NG, Costa RH. The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3 β in the developing murine liver and pancreas. Dev Biol 1997; 192:228-46; PMID:9441664; http://dx.doi.org/10.1006/dbio.1997.8744
  • Jacquemin P, Lemaigre FP, Rousseau GG. 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. Dev Biol 2003; 258:105-16; PMID:12781686; http://dx.doi.org/10.1016/S0012-1606(03)00115-5
  • Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, Hrabe de Angelis M, Lendahl U, Edlund H. Notch signalling controls pancreatic cell differentiation. Nature 1999; 400:877-81; PMID:10476967; http://dx.doi.org/10.1038/23716
  • Jensen J, Pedersen EE, Galante P, Hald J, Heller RS, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD. Control of endodermal endocrine development by Hes-1. Nat Genet 2000; 24, 36-44
  • Jacquemin P, Durviaux SM, Jensen J, Godfraind C, Gradwohl G, Guillemot F, Madsen OD, Carmeliet P, Dewerchin M, Collen D, et al. Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3. Mol Cell Biol 2000; 20:4445-54; PMID:10825208; http://dx.doi.org/10.1128/MCB.20.12.4445-4454.2000
  • Pierreux CE, Poll AV, Kemp CR, Clotman F, Maestro MA, Cordi S, Ferrer J, Leyns L, Rousseau GG, Lemaigre FP. The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse. Gastroenterol 2006; 130:532-41; PMID:16472605; http://dx.doi.org/10.1053/j.gastro.2005.12.005
  • Yamamoto K, Matsuoka TA, Kawashima S, Takebe S, Kubo F, Miyatsuka T, Kaneto H, Shimomura I. A novel function of Onecut1 protein as a negative regulator of MafA gene expression. J Biol Chem 2013; 288:21648-58; PMID:23775071; http://dx.doi.org/10.1074/jbc.M113.481424
  • Zhang H, Ables ET, Pope CF, Washington MK, Hipkens S, Means AL, Path G, Seufert J, Costa RH, Leiter AB, et al. Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal differentiation. Mechan Dev 2009; 126:958-73; PMID:19766716; http://dx.doi.org/10.1016/j.mod.2009.09.006
  • Gannon M, Ray MK, Van Zee K, Rausa F, Costa RH, Wright CV. Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of β cell function. Development 2000; 127:2883-95; PMID:10851133
  • Wu KL, Gannon M, Peshavaria M, Offield MF, Henderson E, Ray M, Marks A, Gamer LW, Wright CV, Stein R. Hepatocyte nuclear factor 3beta is involved in pancreatic β-cell-specific transcription of the pdx-1 gene. Mol Cell Biol 1997; 17:6002-13; PMID:9315659
  • Cockell M, Stolarczyk D, Frutiger S, Hughes GJ, Hagenbuchle O, Wellauer PK. Binding sites for hepatocyte nuclear factor 3 β or 3 gamma and pancreas transcription factor 1 are required for efficient expression of the gene encoding pancreatic α-amylase. Mol Cell Biol 1995; 15:1933-41; PMID:7891687
  • Gao N, LeLay J, Vatamaniuk MZ, Rieck S, Friedman JR, Kaestner KH. Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev 2008; 22:3435-48; PMID:19141476; http://dx.doi.org/10.1101/gad.1752608
  • Lee CS, Sund NJ, Behr R, Herrera PL, Kaestner KH. Foxa2 is required for the differentiation of pancreatic α-cells. Dev Biol 2005; 278:484-95; PMID:15680365; http://dx.doi.org/10.1016/j.ydbio.2004.10.012
  • Kanai-Azuma M, Kanai Y, Gad JM, Tajima Y, Taya C, Kurohmaru M, Sanai Y, Yonekawa H, Yazaki K, Tam PP, et al. Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 2002; 129:2367-79; PMID:11973269
  • Spence JR, Lange AW, Lin SC, Kaestner KH, Lowy AM, Kim I, Whitsett JA, Wells JM. Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. Dev Cell 2009; 17:62-74; PMID:19619492; http://dx.doi.org/10.1016/j.devcel.2009.05.012
  • Jonatan D, Spence JR, Method AM, Kofron M, Sinagoga K, Haataja L, Arvan P, Deutsch GH, Wells JM. Sox17 regulates insulin secretion in the normal and pathologic mouse β cell. PloS One 2014; 9:e104675; PMID:25144761; http://dx.doi.org/10.1371/journal.pone.0104675
  • Guz Y, Montminy MR, Stein R, Leonard J, Gamer LW, Wright CV, Teitelman G. Expression of murine STF-1, a putative insulin gene transcription factor, in β cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 1995; 121:11-8; PMID:7867492
  • 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 1998; 12:1763-8; PMID:9637677; http://dx.doi.org/10.1101/gad.12.12.1763
  • Gannon M, Ables ET, Crawford L, Lowe D, Offield MF, Magnuson MA, Wright CV. Pdx-1 function is specifically required in embryonic β cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol 2008; 314:406-17; PMID:18155690; http://dx.doi.org/10.1016/j.ydbio.2007.10.038
  • Holland AM, Hale MA, Kagami H, Hammer RE, MacDonald RJ. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci USA 2002; 99:12236-41; http://dx.doi.org/10.1073/pnas.192255099
  • Hale MA, Kagami H, Shi L, Holland AM, Elsasser HP, Hammer RE, MacDonald RJ. The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas. Dev Biol 2005; 286:225-37; PMID:16126192; http://dx.doi.org/10.1016/j.ydbio.2005.07.026
  • Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994; 371:606-9; PMID:7935793; http://dx.doi.org/10.1038/371606a0
  • Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997; 17:138-9; PMID:9326926; http://dx.doi.org/10.1038/ng1097-138
  • Nicolino M, Claiborn KC, Senee V, Boland A, Stoffers DA, Julier C. A novel hypomorphic PDX1 mutation responsible for permanent neonatal diabetes with subclinical exocrine deficiency. Diabetes 2010; 59:733-40; PMID:20009086; http://dx.doi.org/10.2337/db09-1284
  • Fujitani Y, Fujitani S, Boyer DF, Gannon M, Kawaguchi Y, Ray M, Shiota M, Stein RW, Magnuson MA, Wright CV. 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; PMID:16418487; http://dx.doi.org/10.1101/gad.1360106
  • Yang YP, Thorel F, Boyer DF, Herrera PL, Wright CV. Context-specific α- to-β-cell reprogramming by forced Pdx1 expression. Genes Dev 2011; 25:1680-5; PMID:21852533; http://dx.doi.org/10.1101/gad.16875711
  • Gerrish K, Gannon M, Shih D, Henderson E, Stoffel M, Wright CV, Stein R. Pancreatic β cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3 β sites. J Biol Chem 2000; 275:3485-92; PMID:10652343; http://dx.doi.org/10.1074/jbc.275.5.3485
  • Gerrish K, Van Velkinburgh JC, Stein R. Conserved transcriptional regulatory domains of the pdx-1 gene. Mol Endocrinol 2004; 18:533-48; PMID:14701942; http://dx.doi.org/10.1210/me.2003-0371
  • Gerrish K, Cissell MA, Stein R. The role of hepatic nuclear factor 1 α and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem 2001; 276:47775-84; PMID:11590182
  • Samaras SE, Cissell MA, Gerrish K, Wright CV, Gannon M, Stein R. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic β cells: role for hepatocyte nuclear factor 3 β and Pax6. Mol Cell Biol 2002; 22:4702-13; PMID:12052878; http://dx.doi.org/10.1128/MCB.22.13.4702-4713.2002
  • Samaras SE, Zhao L, Means A, Henderson E, Matsuoka TA, Stein R. The islet β cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. J Biol Chem 2003; 278:12263-70; PMID:12551916; http://dx.doi.org/10.1074/jbc.M210801200
  • Krapp A, Knofler M, Ledermann B, Burki K, Berney C, Zoerkler N, Hagenbuchle O, Wellauer PK. 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; PMID:9851981; http://dx.doi.org/10.1101/gad.12.23.3752
  • Yoshitomi H, Zaret KS. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 2004; 131:807-17; PMID:14736742; http://dx.doi.org/10.1242/dev.00960
  • Jacquemin P, Yoshitomi H, Kashima Y, Rousseau GG, Lemaigre FP, Zaret KS. An endothelial-mesenchymal relay pathway regulates early phases of pancreas development. Dev Biol 2006; 290:189-99; PMID:16386727; http://dx.doi.org/10.1016/j.ydbio.2005.11.023
  • Cano DA, Soria B, Martin F, Rojas A. Transcriptional control of mammalian pancreas organogenesis. Cell Mol Life Sci 2014; 71:2383-402; PMID:24221136; http://dx.doi.org/10.1007/s00018-013-1510-2
  • Beres TM, Masui T, Swift GH, Shi L, Henke RM, MacDonald RJ. PTF1 is an organ-specific and Notch-independent basic helix-loop-helix complex containing the mammalian suppressor of hairless (RBP-J) or its paralogue, RBP-L. Mol Cell Biol 2006; 26:117-30; PMID:16354684; http://dx.doi.org/10.1128/MCB.26.1.117-130.2006
  • Ehebauer M, Hayward P, Arias AM. Notch, a universal arbiter of cell fate decisions. Science 2006; 314:1414-5; PMID:17138893; http://dx.doi.org/10.1126/science.1134042
  • Masui T, Long Q, Beres TM, Magnuson MA, MacDonald RJ. Early pancreatic development requires the vertebrate suppressor of hairless (RBPJ) in the PTF1 bHLH complex. Genes Dev 2007; 21:2629-43; PMID:17938243; http://dx.doi.org/10.1101/gad.1575207
  • Masui T, Swift GH, Deering T, Shen C, Coats WS, Long Q, Elsasser HP, Magnuson MA, MacDonald RJ. Replacement of Rbpj with Rbpjl in the PTF1 complex controls the final maturation of pancreatic acinar cells. Gastroenterol 2010; 139:270-80; PMID:20398665; http://dx.doi.org/10.1053/j.gastro.2010.04.003
  • Masui T, Swift GH, Hale MA, Meredith DM, Johnson JE, Macdonald RJ. Transcriptional autoregulation controls pancreatic Ptf1a expression during development and adulthood. Mol Cell Biol 2008; 28:5458-68; PMID:18606784; http://dx.doi.org/10.1128/MCB.00549-08
  • Dong PD, Provost E, Leach SD, Stainier DY. Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas. Genes Dev 2008; 22:1445-50; PMID:18519637; http://dx.doi.org/10.1101/gad.1663208
  • Fukuda A, Kawaguchi Y, Furuyama K, Kodama S, Horiguchi M, Kuhara T, Kawaguchi M, Terao M, Doi R, Wright CV, et al. Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice. Diabetes 2008; 57:2421-31; PMID:18591390; http://dx.doi.org/10.2337/db07-1558
  • Ahnfelt-Ronne J, Jorgensen MC, Klinck R, Jensen JN, Fuchtbauer EM, Deering T, MacDonald RJ, Wright CV, Madsen OD, Serup P. Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development 2012; 139:33-45; PMID:22096075; http://dx.doi.org/10.1242/dev.071761
  • Thompson N, Gesina E, Scheinert P, Bucher P, Grapin-Botton A. RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors. Mol Cell Biol 2012; 32:1189-99; PMID:22232429; http://dx.doi.org/10.1128/MCB.06318-11
  • Schaffer AE, Freude KK, Nelson SB, Sander M. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell 2010; 18:1022-9; PMID:20627083; http://dx.doi.org/10.1016/j.devcel.2010.05.015
  • Pan FC, Bankaitis ED, Boyer D, Xu X, Van de Casteele M, Magnuson MA, Heimberg H, Wright CV. Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development 2013; 140:751-64; PMID:23325761; http://dx.doi.org/10.1242/dev.090159
  • Seymour PA, Freude KK, Tran MN, Mayes EE, Jensen J, Kist R, Scherer G, Sander M. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci USA 2007; 104:1865-70; http://dx.doi.org/10.1073/pnas.0609217104
  • Lynn FC, Smith SB, Wilson ME, Yang KY, Nekrep N, German MS. Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci USA 2007; 104:10500-5; http://dx.doi.org/10.1073/pnas.0704054104
  • Seymour PA, Shih HP, Patel NA, Freude KK, Xie R, Lim CJ, Sander M. A Sox9/Fgf feed-forward loop maintains pancreatic organ identity. Development 2012; 139:3363-72; PMID:22874919; http://dx.doi.org/10.1242/dev.078733
  • Decker K, Goldman DC, Grasch CL, Sussel L. Gata6 is an important regulator of mouse pancreas development. Dev Biol 2006; 298:415-29; PMID:16887115; http://dx.doi.org/10.1016/j.ydbio.2006.06.046
  • Watt AJ, Zhao R, Li J, Duncan SA. Development of the mammalian liver and ventral pancreas is dependent on GATA4. BMC Dev Biol 2007; 7:37; PMID:17451603; http://dx.doi.org/10.1186/1471-213X-7-37
  • Ritz-Laser B, Mamin A, Brun T, Avril I, Schwitzgebel VM, Philippe J. The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression. Mol Endocrinol 2005; 19:759-70; PMID:15539431; http://dx.doi.org/10.1210/me.2004-0051
  • Bossard P, Zaret KS. GATA transcription factors as potentiators of gut endoderm differentiation. Development 1998; 125:4909-17; PMID:9811575
  • Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS. Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell 2002; 9:279-89; PMID:11864602; http://dx.doi.org/10.1016/S1097-2765(02)00459-8
  • Zaret KS, Watts J, Xu J, Wandzioch E, Smale ST, Sekiya T. Pioneer factors, genetic competence, and inductive signaling: programming liver and pancreas progenitors from the endoderm. Cold Spring Harb Symp Quant Biol 2008; 73:119-26; PMID:19028990; http://dx.doi.org/10.1101/sqb.2008.73.040
  • Ketola I, Otonkoski T, Pulkkinen MA, Niemi H, Palgi J, Jacobsen CM, Wilson DB, Heikinheimo M. Transcription factor GATA-6 is expressed in the endocrine and GATA-4 in the exocrine pancreas. Mol Cell Endocrinol 2004; 226:51-7; PMID:15489005; http://dx.doi.org/10.1016/j.mce.2004.06.007
  • Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, Soudais C, Leiden JM. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev 1997; 11:1048-60; PMID:9136932; http://dx.doi.org/10.1101/gad.11.8.1048
  • Molkentin JD, Lin Q, Duncan SA, Olson EN. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 1997; 11:1061-72; PMID:9136933; http://dx.doi.org/10.1101/gad.11.8.1061
  • Koutsourakis M, Langeveld A, Patient R, Beddington R, Grosveld F. The transcription factor GATA6 is essential for early extraembryonic development. Development 1999; 126:723-32
  • Xuan S, Borok MJ, Decker KJ, Battle MA, Duncan SA, Hale MA, Macdonald RJ, Sussel L. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. J Clin Invest 2012; 122:3516-28; PMID:23006325; http://dx.doi.org/10.1172/JCI63352
  • Carrasco M, Delgado I, Soria B, Martin F, Rojas A. GATA4 and GATA6 control mouse pancreas organogenesis. J Clin Invest 2012; 122:3504-15; PMID:23006330; http://dx.doi.org/10.1172/JCI63240
  • Rojas A, Schachterle W, Xu SM, Martin F, Black BL. Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer. Dev Biol 2010; 346:346-55; PMID:20692247; http://dx.doi.org/10.1016/j.ydbio.2010.07.032
  • Martinelli P, Canamero M, del Pozo N, Madriles F, Zapata A, Real FX. Gata6 is required for complete acinar differentiation and maintenance of the exocrine pancreas in adult mice. Gut 2013; 62:1481-8; PMID:23002247; http://dx.doi.org/10.1136/gutjnl-2012-303328
  • 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 USA 2000; 97:1607-11; http://dx.doi.org/10.1073/pnas.97.4.1607
  • Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD, German MS. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000; 127:3533-42; PMID:10903178
  • Johansson KA, Dursun U, Jordan N, Gu G, Beermann F, Gradwohl G, Grapin-Botton A. Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types. Dev Cell 2007; 12:457-65; PMID:17336910; http://dx.doi.org/10.1016/j.devcel.2007.02.010
  • Rukstalis JM, Habener JF. Neurogenin3: a master regulator of pancreatic islet differentiation and regeneration. Islets 2009; 1:177-84; PMID:21099270; http://dx.doi.org/10.4161/isl.1.3.9877
  • Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA 2003; 100:14920-5; http://dx.doi.org/10.1073/pnas.2436557100
  • Shih HP, Kopp JL, Sandhu M, Dubois CL, Seymour PA, Grapin-Botton A, Sander M. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. Development 2012; 139:2488-99; PMID:22675211; http://dx.doi.org/10.1242/dev.078634
  • Lee JC, Smith SB, Watada H, Lin J, Scheel D, Wang J, Mirmira RG, German MS. Regulation of the pancreatic pro-endocrine gene neurogenin3. Diabetes 2001; 50:928-36; PMID:11334435; http://dx.doi.org/10.2337/diabetes.50.5.928
  • Wang S, Yan J, Anderson DA, Xu Y, Kanal MC, Cao Z, Wright CV, Gu G. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev Biol 2010; 339:26-37; PMID:20025861; http://dx.doi.org/10.1016/j.ydbio.2009.12.009
  • Desgraz R, Herrera PL. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development 2009; 136:3567-74; PMID:19793886; http://dx.doi.org/10.1242/dev.039214
  • Smith SB, Watada H, German MS. Neurogenin3 activates the islet differentiation program while repressing its own expression. Mol Endocrinol 2004; 18:142-9; PMID:14576336; http://dx.doi.org/10.1210/me.2003-0037
  • Wang S, Hecksher-Sorensen J, Xu Y, Zhao A, Dor Y, Rosenberg L, Serup P, Gu G. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Dev Biol 2008; 317:531-40; PMID:18394599; http://dx.doi.org/10.1016/j.ydbio.2008.02.052
  • Ejarque M, Cervantes S, Pujadas G, Tutusaus A, Sanchez L, Gasa R. Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. JBiol Chem 2013; 288:11705-17; PMID:23471965; http://dx.doi.org/10.1074/jbc.M112.388173
  • Smith SB, Gasa R, Watada H, Wang J, Griffen SC, German MS. Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. J Biol Chem 2003; 278:38254-9; PMID:12837760; http://dx.doi.org/10.1074/jbc.M302229200
  • Huang HP, Liu M, El-Hodiri HM, Chu K, Jamrich M, Tsai MJ. Regulation of the pancreatic islet-specific gene BETA2 (NeuroD) by neurogenin 3. Mol Cell Biol 2000; 20:3292-307; PMID:10757813; http://dx.doi.org/10.1128/MCB.20.9.3292-3307.2000
  • Naya FJ, Huang HP, Qiu Y, Mutoh H, DeMayo FJ, Leiter AB, Tsai MJ. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 1997; 11:2323-34; PMID:9308961; http://dx.doi.org/10.1101/gad.11.18.2323
  • Smith SB, Qu HQ, Taleb N, Kishimoto NY, Scheel DW, Lu Y, Patch AM, Grabs R, Wang J, Lynn FC, et al. Rfx6 directs islet formation and insulin production in mice and humans. Nature 2010; 463:775-80; PMID:20148032; http://dx.doi.org/10.1038/nature08748
  • Gouzi M, Kim YH, Katsumoto K, Johansson K, Grapin-Botton A. Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development. Dev Dynam 2011; 240:589-604; PMID:21287656; http://dx.doi.org/10.1002/dvdy.22544
  • Prasadan K, Tulachan S, Guo P, Shiota C, Shah S, Gittes G. Endocrine-committed progenitor cells retain their differentiation potential in the absence of neurogenin-3 expression. Biochem Biophys Res Commun 2010; 396:1036-41; PMID:20471370; http://dx.doi.org/10.1016/j.bbrc.2010.05.058
  • Magenheim J, Klein AM, Stanger BZ, Ashery-Padan R, Sosa-Pineda B, Gu G, Dor Y. Ngn3(+) endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium. Dev Biol 2011; 359:26-36; PMID:21888903; http://dx.doi.org/10.1016/j.ydbio.2011.08.006
  • Piccand J, Meunier A, Merle C, Jia Z, Barnier JV, Gradwohl G. Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice. Diabetes 2014; 63:203-15; PMID:24163148; http://dx.doi.org/10.2337/db13-0384
  • Osipovich AB, Long Q, Manduchi E, Gangula R, Hipkens SB, Schneider J, Okubo T, Stoeckert CJ, Jr., Takada S, Magnuson MA. Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3. Development 2014; 141:2939-49; PMID:25053427; http://dx.doi.org/10.1242/dev.104810
  • Mutoh H, Fung BP, Naya FJ, Tsai MJ, Nishitani J, Leiter AB. The basic helix-loop-helix transcription factor BETA2/NeuroD is expressed in mammalian enteroendocrine cells and activates secretin gene expression. Proc Natl Acad Sci USA 1997; 94:3560-4; http://dx.doi.org/10.1073/pnas.94.8.3560
  • Gu C, Stein GH, Pan N, Goebbels S, Hornberg H, Nave KA, Herrera P, White P, Kaestner KH, Sussel L, et al. Pancreatic β cells require NeuroD to achieve and maintain functional maturity. Cell Metab 2010; 11:298-310; PMID:20374962; http://dx.doi.org/10.1016/j.cmet.2010.03.006
  • Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003; 9:596-603; PMID:12704384; http://dx.doi.org/10.1038/nm867
  • Noguchi H, Xu G, Matsumoto S, Kaneto H, Kobayashi N, Bonner-Weir S, Hayashi S. Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology. Cell Transplantation 2006; 15:929-38; PMID:17299998; http://dx.doi.org/10.3727/000000006783981431
  • Kaneto H, Matsuoka TA, Katakami N, Matsuhisa M. Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate β-cells. Curr Med Chem 2009; 16:3144-51; PMID:19689288; http://dx.doi.org/10.2174/092986709788802980
  • Aftab S, Semenec L, Chu JS, Chen N. Identification and characterization of novel human tissue-specific RFX transcription factors. BMC Evol Biol 2008; 8:226; PMID:18673564; http://dx.doi.org/10.1186/1471-2148-8-226
  • Feng C, Xu W, Zuo Z. Knockout of the regulatory factor X1 gene leads to early embryonic lethality. Biochem Biophys Res Commun 2009; 386:715-7; PMID:19559676; http://dx.doi.org/10.1016/j.bbrc.2009.06.111
  • Ait-Lounis A, Baas D, Barras E, Benadiba C, Charollais A, Nlend Nlend R, Liegeois D, Meda P, Durand B, Reith W. Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas. Diabetes 2007; 56:950-9; PMID:17229940; http://dx.doi.org/10.2337/db06-1187
  • Soyer J, Flasse L, Raffelsberger W, Beucher A, Orvain C, Peers B, Ravassard P, Vermot J, Voz ML, Mellitzer G, et al. Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development 2010; 137:203-12; PMID:20040487; http://dx.doi.org/10.1242/dev.041673
  • Piccand J, Strasser P, Hodson DJ, Meunier A, Ye T, Keime C, Birling MC, Rutter GA, Gradwohl G. Rfx6 maintains the functional identity of adult pancreatic β cells. Cell Rep 2014; 9:2219-32; PMID:25497096; http://dx.doi.org/10.1016/j.celrep.2014.11.033
  • Chandra V, Albagli-Curiel O, Hastoy B, Piccand J, Randriamampita C, Vaillant E, Cave H, Busiah K, Froguel P, Vaxillaire M, et al. RFX6 regulates insulin secretion by modulating Ca(2+) homeostasis in human β cells. Cell Rep 2014; 9:2206-18; PMID:25497100; http://dx.doi.org/10.1016/j.celrep.2014.11.010
  • Du A, Hunter CS, Murray J, Noble D, Cai CL, Evans SM, Stein R, May CL. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes 2009; 58:2059-69; PMID:19502415; http://dx.doi.org/10.2337/db08-0987
  • May CL. The role of Islet-1 in the endocrine pancreas: lessons from pancreas specific Islet-1 deficient mice. Islets 2010; 2:121-3; PMID:21099304; http://dx.doi.org/10.4161/isl.2.2.10908
  • Liu J, Hunter CS, Du A, Ediger B, Walp E, Murray J, Stein R, May CL. Islet-1 regulates Arx transcription during pancreatic islet α-cell development. J Biol Chem 2011; 286:15352-60; PMID:21388963; http://dx.doi.org/10.1074/jbc.M111.231670
  • Hunter CS, Dixit S, Cohen T, Ediger B, Wilcox C, Ferreira M, Westphal H, Stein R, May CL. Islet α-, β-, and δ-cell development is controlled by the Ldb1 coregulator, acting primarily with the islet-1 transcription factor. Diabetes 2013; 62:875-86; PMID:23193182; http://dx.doi.org/10.2337/db12-0952
  • Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic β cells. Development 1998; 125:2213-21; PMID:9584121
  • Mastracci TL, Anderson KR, Papizan JB, Sussel L. Regulation of NeuroD1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas. PLoS Genet 2013; 9:e1003278; PMID:23408910; http://dx.doi.org/10.1371/journal.pgen.1003278
  • Chao CS, Loomis ZL, Lee JE, Sussel L. Genetic identification of a novel NeuroD1 function in the early differentiation of islet α, PP and epsilon cells. Dev Biol 2007; 312:523-32; PMID:17988662; http://dx.doi.org/10.1016/j.ydbio.2007.09.057
  • Kordowich S, Collombat P, Mansouri A, Serup P. Arx and Nkx2.2 compound deficiency redirects pancreatic α- and β-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC Dev Biol 2011; 11:52; PMID:21880149; http://dx.doi.org/10.1186/1471-213X-11-52
  • Mastracci TL, Wilcox CL, Arnes L, Panea C, Golden JA, May CL, Sussel L. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Dev Biol 2011; 359:1-11; PMID:21856296; http://dx.doi.org/10.1016/j.ydbio.2011.08.001
  • Raum JC, Gerrish K, Artner I, Henderson E, Guo M, Sussel L, Schisler JC, Newgard CB, Stein R. FoxA2, Nkx2.2, and PDX-1 regulate islet β-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site. Mol Cell Biol 2006; 26:5735-43; PMID:16847327; http://dx.doi.org/10.1128/MCB.00249-06
  • Cissell MA, Zhao L, Sussel L, Henderson E, Stein R. Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2. J Biol Chem 2003; 278:751-6; PMID:12426319; http://dx.doi.org/10.1074/jbc.M205905200
  • Oster A, Jensen J, Edlund H, Larsson LI. Homeobox gene product Nkx 6.1 immunoreactivity in nuclei of endocrine cells of rat and mouse stomach. J Histochem Cytochem 1998; 46:717-21; PMID:9603782; http://dx.doi.org/10.1177/002215549804600603
  • Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, Schwitzgebel V, Hayes-Jordan A, German M. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas. Development 2000; 127:5533-40; PMID:11076772
  • Gauthier BR, Gosmain Y, Mamin A, Philippe J. The β-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6. Biochem J 2007; 403:593-601; PMID:17263687; http://dx.doi.org/10.1042/BJ20070053
  • Schisler JC, Jensen PB, Taylor DG, Becker TC, Knop FK, Takekawa S, German M, Weir GC, Lu D, Mirmira RG, et al. The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet β cells. Proc Natl Acad Sci USA 2005; 102:7297-302; http://dx.doi.org/10.1073/pnas.0502168102
  • Nelson SB, Schaffer AE, Sander M. The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting β-cell fate specification in Pdx1+ pancreatic progenitor cells. Development 2007; 134:2491-500; PMID:17537793; http://dx.doi.org/10.1242/dev.002691
  • Henseleit KD, Nelson SB, Kuhlbrodt K, Hennings JC, Ericson J, Sander M. NKX6 transcription factor activity is required for α- and β-cell development in the pancreas. Development 2005; 132:3139-49; PMID:15944193; http://dx.doi.org/10.1242/dev.01875
  • Schaffer AE, Taylor BL, Benthuysen JR, Liu J, Thorel F, Yuan W, Jiao Y, Kaestner KH, Herrera PL, Magnuson MA, et al. Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic β cell identity. PLoS Genet 2013; 9:e1003274; PMID:23382704; http://dx.doi.org/10.1371/journal.pgen.1003274
  • Collombat P, Hecksher-Sorensen J, Broccoli V, Krull J, Ponte I, Mundiger T, Smith J, Gruss P, Serup P, Mansouri A. The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the α- and β-cell lineages in the mouse endocrine pancreas. Development 2005; 132:2969-80; PMID:15930104; http://dx.doi.org/10.1242/dev.01870
  • Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 2003; 17:2591-603; PMID:14561778; http://dx.doi.org/10.1101/gad.269003
  • Kordowich S, Mansouri A, Collombat P. Reprogramming into pancreatic endocrine cells based on developmental cues. Mol Cell Endocrinol 2010; 315:11-8; PMID:19897012; http://dx.doi.org/10.1016/j.mce.2009.10.015
  • Dohrmann C, Gruss P, Lemaire L. Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas. Mech Dev 2000; 92:47-54; PMID:10704887; http://dx.doi.org/10.1016/S0925-4773(99)00324-X
  • Smith SB, Ee HC, Conners JR, German MS. Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. Mol Cell Biol 1999; 19:8272-80; PMID:10567552
  • 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. Nature 1997; 386:399-402; PMID:9121556; http://dx.doi.org/10.1038/386399a0
  • Greenwood AL, Li S, Jones K, Melton DA. Notch signaling reveals developmental plasticity of Pax4(+) pancreatic endocrine progenitors and shunts them to a duct fate. Mech Dev 2007; 124:97-107; PMID:17196797; http://dx.doi.org/10.1016/j.mod.2006.11.002
  • Wang Q, Elghazi L, Martin S, Martins I, Srinivasan RS, Geng X, Sleeman M, Collombat P, Houghton J, Sosa-Pineda B. Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Dev Dyn 2008; 237:51-61; PMID:18058910; http://dx.doi.org/10.1002/dvdy.21379
  • Ritz-Laser B, Estreicher A, Gauthier BR, Mamin A, Edlund H, Philippe J. The pancreatic β-cell-specific transcription factor Pax-4 inhibits glucagon gene expression through Pax-6. Diabetologia 2002; 45:97-107; PMID:11845228; http://dx.doi.org/10.1007/s125-002-8249-9
  • Wang J, Elghazi L, Parker SE, Kizilocak H, Asaano M, Sussel L, Sosa-Pineda B. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic β-cell differentiation. Dev Biol 2004; 266:178-89; PMID:14729487; http://dx.doi.org/10.1016/j.ydbio.2003.10.018
  • Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into α and subsequently β cells. Cell 2009; 138:449-62; PMID:19665969; http://dx.doi.org/10.1016/j.cell.2009.05.035
  • 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 1994; 8:929-38; PMID:7984154
  • 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. Nature 1997; 387:406-9; PMID:9163426; http://dx.doi.org/10.1038/387406a0
  • Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, German MS. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 1997; 11:1662-73; PMID:9224716; http://dx.doi.org/10.1101/gad.11.13.1662
  • Ashery-Padan R, Zhou X, Marquardt T, Herrera P, Toube L, Berry A, Gruss P. Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes. Dev Biol 2004; 269:479-88; PMID:15110714; http://dx.doi.org/10.1016/j.ydbio.2004.01.040
  • Heller RS, Stoffers DA, Liu A, Schedl A, Crenshaw EB, 3rd, Madsen OD, Serup P. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol 2004; 268:123-34; PMID:15031110; http://dx.doi.org/10.1016/j.ydbio.2003.12.008
  • Heller RS, Jenny M, Collombat P, Mansouri A, Tomasetto C, Madsen OD, Mellitzer G, Gradwohl G, Serup P. Genetic determinants of pancreatic epsilon-cell development. Dev Biol 2005; 286:217-24; PMID:16122727; http://dx.doi.org/10.1016/j.ydbio.2005.06.041
  • Kang HS, ZeRuth G, Lichti-Kaiser K, Vasanth S, Yin Z, Kim YS, Jetten AM. Gli-similar (Glis) Kruppel-like zinc finger proteins: insights into their physiological functions and critical roles in neonatal diabetes and cystic renal disease. Histol Histopathol 2010; 25:1481-96; PMID:20865670
  • Lichti-Kaiser K, ZeRuth G, Kang HS, Vasanth S, Jetten AM. Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease. Vitam Horm 2012; 88:141-71; PMID:22391303; http://dx.doi.org/10.1016/B978-0-12-394622-5.00007-9
  • Watanabe N, Hiramatsu K, Miyamoto R, Yasuda K, Suzuki N, Oshima N, Kiyonari H, Shiba D, Nishio S, Mochizuki T, et al. A murine model of neonatal diabetes mellitus in Glis3-deficient mice. FEBS Letters 2009; 583:2108-13; PMID:19481545; http://dx.doi.org/10.1016/j.febslet.2009.05.039
  • Kang HS, Kim YS, ZeRuth G, Beak JY, Gerrish K, Kilic G, Sosa-Pineda B, Jensen J, Pierreux CE, Lemaigre FP, et al. Transcription factor Glis3, a novel critical player in the regulation of pancreatic β-cell development and insulin gene expression. Mol Cell Biol 2009; 29:6366-79; PMID:19805515; http://dx.doi.org/10.1128/MCB.01259-09
  • Yang Y, Chang BH, Yechoor V, Chen W, Li L, Tsai MJ, Chan L. The Kruppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice. Diabetologia 2011; 54:2595-605; PMID:21786021; http://dx.doi.org/10.1007/s00125-011-2255-9
  • Yang Y, Chang BH, Samson SL, Li MV, Chan L. The Kruppel-like zinc finger protein Glis3 directly and indirectly activates insulin gene transcription. Nucleic Acids Res 2009; 37:2529-38; PMID:19264802; http://dx.doi.org/10.1093/nar/gkp122
  • Yang Y, Chang BH, Chan L. Sustained expression of the transcription factor GLIS3 is required for normal β cell function in adults. EMBO Mol Med 2013; 5:92-104; PMID:23197416; http://dx.doi.org/10.1002/emmm.201201398
  • ZeRuth GT, Takeda Y, Jetten AM. The Kruppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. Mol Endocrinol 2013; 27:1692-705; PMID:23927931; http://dx.doi.org/10.1210/me.2013-1117
  • Kim YS, Kang HS, Takeda Y, Hom L, Song HY, Jensen J, Jetten AM. Glis3 regulates neurogenin 3 expression in pancreatic β-cells and interacts with its activator, Hnf6. Mol Cells 2012; 34:193-200; PMID:22820919; http://dx.doi.org/10.1007/s10059-012-0109-z
  • Artner I, Hang Y, Mazur M, Yamamoto T, Guo M, Lindner J, Magnuson MA, Stein R. MafA and MafB regulate genes critical to β-cells in a unique temporal manner. Diabetes 2010; 59:2530-9; PMID:20627934; http://dx.doi.org/10.2337/db10-0190
  • Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner-Weir S, Sharma A. A switch from MafB to MafA expression accompanies differentiation to pancreatic β-cells. Dev Biol 2006; 293:526-39; PMID:16580660; http://dx.doi.org/10.1016/j.ydbio.2006.02.028
  • Hang Y, Stein R. MafA and MafB activity in pancreatic β cells. Trends Endocrinol Metab 2011; 22:364-73; PMID:21719305; http://dx.doi.org/10.1016/j.tem.2011.05.003
  • Artner I, Blanchi B, Raum JC, Guo M, Kaneko T, Cordes S, Sieweke M, Stein R. MafB is required for islet β cell maturation. Proc Natl Acad Sci USA 2007; 104:3853-8; http://dx.doi.org/10.1073/pnas.0700013104
  • Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa K, et al. MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol 2005; 25:4969-76; PMID:15923615; http://dx.doi.org/10.1128/MCB.25.12.4969-4976.2005
  • Hang Y, Yamamoto T, Benninger RK, Brissova M, Guo M, Bush W, Piston DW, Powers AC, Magnuson M, Thurmond DC, et al. The MafA transcription factor becomes essential to islet β-cells soon after birth. Diabetes 2014; 63:1994-2005; PMID:24520122; http://dx.doi.org/10.2337/db13-1001
  • Hu He K, Juhl K, Karadimos M, El Khattabi I, Fitzpatrick C, Bonner-Weir S, Sharma A. Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA. Dev Biol 2014; 385:2-12.; PMID:24183936; http://dx.doi.org/10.1016/j.ydbio.2013.10.024
  • Willet SG, Hale MA, Grapin-Botton A, Magnuson MA, MacDonald RJ, Wright CV. Dominant and context-specific control of endodermal organ allocation by Ptf1a. Development 2014; 141:4385-94; PMID:25371369; http://dx.doi.org/10.1242/dev.114165
  • Hale MA, Swift GH, Hoang CQ, Deering TG, Masui T, Lee YK, Xue J, MacDonald RJ. The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis. Development 2014; 141:3123-33; PMID:25063451; http://dx.doi.org/10.1242/dev.109405
  • Benitez CM, Qu K, Sugiyama T, Pauerstein PT, Liu Y, Tsai J, Gu X, Ghodasara A, Arda HE, Zhang J, et al. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development. PLoS Genet 2014; 10:e1004645; PMID:25330008; http://dx.doi.org/10.1371/journal.pgen.1004645
  • Dorrell C, Tarlow B, Wang Y, Canaday PS, Haft A, Schug J, Streeter PR, Finegold MJ, Shenje LT, Kaestner KH, et al. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar. Stem Cell Res 2014; 13:275-83; PMID:25151611; http://dx.doi.org/10.1016/j.scr.2014.07.006
  • Afelik S, Pool B, Schmerr M, Penton C, Jensen J. Wnt7b is required for epithelial progenitor growth and operates during epithelial-to-mesenchymal signaling in pancreatic development. Dev Biol 2015; 399:204-17; PMID:25576928; http://dx.doi.org/10.1016/j.ydbio.2014.12.031
  • Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart N, Cunningham J, Agulnick AD, D'Amour KA, Carpenter MK, Baetge, EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26:443-52; PMID:18288110; http://dx.doi.org/10.1038/nbt1393
  • Ohneda K, EE H, German M. Regulation of insulin gene transcription. Seminars Cell Dev Biol 2000; 11:227-33; http://dx.doi.org/10.1006/scdb.2000.0171
  • Abdellatif AM, Ogata K, Kudo T, Xiafukaiti G, Chang YH, Katoh MC, El-Morsy SE, Oishi H, Takahashi S. Role of large MAF transcription factors in the mouse endocrine pancreas. Exp Anim 2015; 64(3):305-12; PMID:25912440

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.