title: Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies.
abstract: Diabetes is a disease that could be treated more effectively with a better understanding of pancreas development. This review examines the role of master regulator genes driving crucial steps in pancreas development, from foregut specification to differentiation of the five endocrine cell types. The roles of Pdx1, Ptf1a, and Ngn3 are particularly examined as they are both necessary and sufficient for promoting pancreatic cell fates (Pdx1, Ptf1a) and endocrine cell development (Ngn3). The roles of Arx and Pax4 are studied as they compose part of the regulatory mechanism balancing development of different types of endocrine cells within the iselts and promote the development of alpha/PP and beta/delta cell progenitors, respectively. The roles of the aforementioned genes, and the consequences of misexpression of them for functionality of the pancreas, are examined through recent studies in model organisms, particularly Xenopus and zebrafish. Recent developments in cell replacement therapy research are also covered, concentrating on stem cell research (coaxing both adult and embryonic stem cells toward a beta cell fate) and transdifferentiation (generating beta cells from other differentiated cell types).
authors.affiliation: Laboratory of Molecular Organogenesis, Institut de Recherches Cliniques de Montréal, Québec, Canada.
authors.forename: E J
authors.initials: EJ
authors.lastname: Pearl
authors.forename: M E
authors.initials: ME
authors.lastname: Horb
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
references.citation: J Clin Invest. 2007 Apr;117(4):961-70
references.pmid: 17404619
references.citation: Mol Cell Biol. 2007 Jun;27(11):4093-104
references.pmid: 17403901
references.citation: Mol Endocrinol. 1994 Jun;8(6):806-16
references.pmid: 7935494
references.citation: Nat Biotechnol. 2006 Nov;24(11):1392-401
references.pmid: 17053790
references.citation: Front Biosci. 2008 May 01;13:5824-37
references.pmid: 18508625
references.citation: Genes Dev. 2007 Oct 15;21(20):2629-43
references.pmid: 17938243
references.citation: Dev Biol. 2003 Sep 1;261(1):197-208
references.pmid: 12941629
references.citation: Curr Opin Genet Dev. 2001 Oct;11(5):581-6
references.pmid: 11532402
references.citation: Development. 1996 Mar;122(3):983-95
references.pmid: 8631275
references.citation: J Pediatr Surg. 2008 Feb;43(2):274-8
references.pmid: 18280273
references.citation: Dev Cell. 2008 Apr;14(4):582-93
references.pmid: 18410733
references.citation: Genes Dev. 2006 Jun 1;20(11):1435-40
references.pmid: 16751181
references.citation: Nat Biotechnol. 2003 Jul;21(7):763-70
references.pmid: 12819790
references.citation: Biochem Soc Trans. 2008 Jun;36(Pt 3):353-6
references.pmid: 18481956
references.citation: Nature. 1997 Mar 27;386(6623):399-402
references.pmid: 9121556
references.citation: J Autoimmun. 2007 Mar-May;28(2-3):134-42
references.pmid: 17383157
references.citation: Lab Invest. 2006 Jan;86(1):83-93
references.pmid: 16294197
references.citation: J Tissue Eng Regen Med. 2008 Jun;2(4):169-83
references.pmid: 18493906
references.citation: Nature. 1999 Aug 26;400(6747):877-81
references.pmid: 10476967
references.citation: Dev Biol. 2002 Apr 1;244(1):75-84
references.pmid: 11900460
references.citation: Diabetes Res Clin Pract. 2008 Mar;79(3):389-99
references.pmid: 17854943
references.citation: Dev Cell. 2007 Mar;12(3):457-65
references.pmid: 17336910
references.citation: Dev Biol. 2007 Apr 15;304(2):786-99
references.pmid: 17320068
references.citation: Mol Cell Biol. 2000 Jun;20(12):4445-54
references.pmid: 10825208
references.citation: EMBO J. 1993 Nov;12(11):4251-9
references.pmid: 7901001
references.citation: Development. 1996 May;122(5):1409-16
references.pmid: 8625829
references.citation: Gastroenterology. 2007 Feb;132(2):745-62
references.pmid: 17258745
references.citation: Physiol Rev. 2007 Oct;87(4):1343-75
references.pmid: 17928586
references.citation: Nat Genet. 2002 Sep;32(1):128-34
references.pmid: 12185368
references.citation: Dev Biol. 2001 Jan 1;229(1):188-202
references.pmid: 11133163
references.citation: Dev Dyn. 2008 Jan;237(1):51-61
references.pmid: 18058910
references.citation: Nature. 1994 Oct 13;371(6498):606-9
references.pmid: 7935793
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10500-5
references.pmid: 17563382
references.citation: Dev Dyn. 2004 Jan;229(1):176-200
references.pmid: 14699589
references.citation: Can Med Assoc J. 1922 Mar;12(3):141-6
references.pmid: 20314060
references.citation: Dev Growth Differ. 2000 Dec;42(6):593-602
references.pmid: 11142681
references.citation: Stem Cells Dev. 2007 Aug;16(4):561-78
references.pmid: 17784830
references.citation: Mech Dev. 2003 Jan;120(1):65-80
references.pmid: 12490297
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2924-9
references.pmid: 14970313
references.citation: Biochem Biophys Res Commun. 2008 Jun 20;371(1):132-7
references.pmid: 18420028
references.citation: Development. 2002 May;129(10):2447-57
references.pmid: 11973276
references.citation: Mech Dev. 2003 Jan;120(1):5-18
references.pmid: 12490292
references.citation: Mech Dev. 2007 Aug;124(7-8):518-31
references.pmid: 17643968
references.citation: Genes Dev. 2003 Oct 15;17(20):2591-603
references.pmid: 14561778
references.citation: Genesis. 2001 Jul;30(3):137-40
references.pmid: 11477692
references.citation: Nat Genet. 2004 Dec;36(12):1301-5
references.pmid: 15543146
references.citation: Regul Pept. 2002 Jul 15;107(1-3):63-9
references.pmid: 12137967
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1607-11
references.pmid: 10677506
references.citation: Stem Cells. 2007 Nov;25(11):2837-44
references.pmid: 17615265
references.citation: Stem Cells Dev. 2007 Oct;16(5):757-70
references.pmid: 17999597
references.citation: Mech Dev. 2003 Jan;120(1):45-57
references.pmid: 12490295
references.citation: Development. 2004 Sep;131(17):4213-24
references.pmid: 15280211
references.citation: Dev Biol. 2004 Oct 15;274(2):491-503
references.pmid: 15570689
references.citation: Trends Mol Med. 2007 Apr;13(4):164-73
references.pmid: 17307397
references.citation: J Clin Invest. 2006 Jun;116(6):1484-93
references.pmid: 16710472
references.citation: Semin Cell Dev Biol. 2006 Feb;17(1):133-45
references.pmid: 16337415
references.citation: Development. 1989 Apr;105(4):787-94
references.pmid: 2574662
references.citation: Curr Biol. 2003 Jan 21;13(2):105-15
references.pmid: 12546783
references.citation: Dev Biol. 2005 Oct 1;286(1):217-24
references.pmid: 16122727
references.citation: Endocr Rev. 2007 Oct;28(6):685-705
references.pmid: 17881611
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1865-70
references.pmid: 17267606
references.citation: Diabetologia. 2007 Jan;50(1):121-30
references.pmid: 17131142
references.citation: Dev Biol. 2008 Apr 1;316(1):74-86
references.pmid: 18294628
references.citation: APMIS. 2005 Nov-Dec;113(11-12):858-75
references.pmid: 16480455
references.citation: Nat Genet. 1997 Jan;15(1):106-10
references.pmid: 8988180
references.citation: Genes Dev. 1998 Jun 1;12(11):1705-13
references.pmid: 9620856
references.citation: Hepatology. 2007 Sep;46(3):898-905
references.pmid: 17705277
references.citation: Development. 2008 Feb;135(3):451-61
references.pmid: 18094028
references.citation: Lab Invest. 2006 Aug;86(8):829-41
references.pmid: 16732298
references.citation: Diabetes. 2000 Feb;49(2):225-32
references.pmid: 10868939
references.citation: Dev Biol. 2004 Jul 1;271(1):144-60
references.pmid: 15196957
references.citation: Development. 2007 Feb;134(3):427-38
references.pmid: 17185316
references.citation: EMBO J. 1994 Mar 1;13(5):1145-56
references.pmid: 7907546
references.citation: Dev Biol. 2003 Jun 1;258(1):105-16
references.pmid: 12781686
references.citation: Nat Biotechnol. 2006 Dec;24(12):1481-3
references.pmid: 17160042
references.citation: Horm Metab Res. 2008 Feb;40(2):147-54
references.pmid: 18283633
references.citation: Diabetes. 2007 Apr;56(4):950-9
references.pmid: 17229940
references.citation: Dev Biol. 2004 Apr 1;268(1):174-84
references.pmid: 15031114
references.citation: Curr Biol. 2001 Sep 4;11(17):1358-63
references.pmid: 11553330
references.citation: J Clin Endocrinol Metab. 2003 Sep;88(9):4398-406
references.pmid: 12970316
references.citation: Genes Dev. 2006 Sep 1;20(17):2465-78
references.pmid: 16951258
references.citation: Dev Dyn. 2000 Aug;218(4):615-27
references.pmid: 10906780
references.citation: Dev Biol. 2005 Aug 15;284(2):399-411
references.pmid: 16026781
references.citation: Nat Rev Mol Cell Biol. 2002 Mar;3(3):187-94
references.pmid: 11994739
references.citation: Front Biosci. 2008 May 01;13:6170-82
references.pmid: 18508651
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17438-43
references.pmid: 17088535
references.citation: Development. 2007 Jun;134(12):2207-17
references.pmid: 17507400
references.citation: Mech Dev. 2006 Jul;123(7):501-12
references.pmid: 16822656
references.citation: Mol Endocrinol. 1993 Oct;7(10):1275-83
references.pmid: 7505393
references.citation: Dev Dyn. 2005 Apr;232(4):950-7
references.pmid: 15739227
references.citation: Development. 2005 Jul;132(13):2969-80
references.pmid: 15930104
references.citation: EMBO J. 2006 Mar 22;25(6):1344-52
references.pmid: 16511571
references.citation: Transl Res. 2008 Jun;151(6):293-302
references.pmid: 18514140
references.citation: Development. 2000 Aug;127(16):3533-42
references.pmid: 10903178
references.citation: Dev Genes Evol. 2004 Sep;214(9):432-41
references.pmid: 15322880
references.citation: Genes Dev. 1998 Dec 1;12(23):3752-63
references.pmid: 9851981
references.citation: Genes Dev. 2006 Jun 1;20(11):1441-6
references.pmid: 16751182
references.citation: Diabetes Res Clin Pract. 2007 Oct;78(1):1-7
references.pmid: 17349714