Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies.
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).
Pearl
E J
EJ
Laboratory of Molecular Organogenesis, Institut de Recherches Cliniques de Montréal, Québec, Canada.
Horb
M E
ME
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
D014157:Transcription Factors
J Clin Invest. 2007 Apr;117(4):961-70
17404619
Mol Cell Biol. 2007 Jun;27(11):4093-104
17403901
Mol Endocrinol. 1994 Jun;8(6):806-16
7935494
Nat Biotechnol. 2006 Nov;24(11):1392-401
17053790
Front Biosci. 2008 May 01;13:5824-37
18508625
Genes Dev. 2007 Oct 15;21(20):2629-43
17938243
Dev Biol. 2003 Sep 1;261(1):197-208
12941629
Curr Opin Genet Dev. 2001 Oct;11(5):581-6
11532402
Development. 1996 Mar;122(3):983-95
8631275
J Pediatr Surg. 2008 Feb;43(2):274-8
18280273
Dev Cell. 2008 Apr;14(4):582-93
18410733
Genes Dev. 2006 Jun 1;20(11):1435-40
16751181
Nat Biotechnol. 2003 Jul;21(7):763-70
12819790
Biochem Soc Trans. 2008 Jun;36(Pt 3):353-6
18481956
Nature. 1997 Mar 27;386(6623):399-402
9121556
J Autoimmun. 2007 Mar-May;28(2-3):134-42
17383157
Lab Invest. 2006 Jan;86(1):83-93
16294197
J Tissue Eng Regen Med. 2008 Jun;2(4):169-83
18493906
Nature. 1999 Aug 26;400(6747):877-81
10476967
Dev Biol. 2002 Apr 1;244(1):75-84
11900460
Diabetes Res Clin Pract. 2008 Mar;79(3):389-99
17854943
Dev Cell. 2007 Mar;12(3):457-65
17336910
Dev Biol. 2007 Apr 15;304(2):786-99
17320068
Mol Cell Biol. 2000 Jun;20(12):4445-54
10825208
EMBO J. 1993 Nov;12(11):4251-9
7901001
Development. 1996 May;122(5):1409-16
8625829
Gastroenterology. 2007 Feb;132(2):745-62
17258745
Physiol Rev. 2007 Oct;87(4):1343-75
17928586
Nat Genet. 2002 Sep;32(1):128-34
12185368
Dev Biol. 2001 Jan 1;229(1):188-202
11133163
Dev Dyn. 2008 Jan;237(1):51-61
18058910
Nature. 1994 Oct 13;371(6498):606-9
7935793
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10500-5
17563382
Dev Dyn. 2004 Jan;229(1):176-200
14699589
Can Med Assoc J. 1922 Mar;12(3):141-6
20314060
Dev Growth Differ. 2000 Dec;42(6):593-602
11142681
Stem Cells Dev. 2007 Aug;16(4):561-78
17784830
Mech Dev. 2003 Jan;120(1):65-80
12490297
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2924-9
14970313
Biochem Biophys Res Commun. 2008 Jun 20;371(1):132-7
18420028
Development. 2002 May;129(10):2447-57
11973276
Mech Dev. 2003 Jan;120(1):5-18
12490292
Mech Dev. 2007 Aug;124(7-8):518-31
17643968
Genes Dev. 2003 Oct 15;17(20):2591-603
14561778
Genesis. 2001 Jul;30(3):137-40
11477692
Nat Genet. 2004 Dec;36(12):1301-5
15543146
Regul Pept. 2002 Jul 15;107(1-3):63-9
12137967
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1607-11
10677506
Stem Cells. 2007 Nov;25(11):2837-44
17615265
Stem Cells Dev. 2007 Oct;16(5):757-70
17999597
Mech Dev. 2003 Jan;120(1):45-57
12490295
Development. 2004 Sep;131(17):4213-24
15280211
Dev Biol. 2004 Oct 15;274(2):491-503
15570689
Trends Mol Med. 2007 Apr;13(4):164-73
17307397
J Clin Invest. 2006 Jun;116(6):1484-93
16710472
Semin Cell Dev Biol. 2006 Feb;17(1):133-45
16337415
Development. 1989 Apr;105(4):787-94
2574662
Curr Biol. 2003 Jan 21;13(2):105-15
12546783
Dev Biol. 2005 Oct 1;286(1):217-24
16122727
Endocr Rev. 2007 Oct;28(6):685-705
17881611
Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1865-70
17267606
Diabetologia. 2007 Jan;50(1):121-30
17131142
Dev Biol. 2008 Apr 1;316(1):74-86
18294628
APMIS. 2005 Nov-Dec;113(11-12):858-75
16480455
Nat Genet. 1997 Jan;15(1):106-10
8988180
Genes Dev. 1998 Jun 1;12(11):1705-13
9620856
Hepatology. 2007 Sep;46(3):898-905
17705277
Development. 2008 Feb;135(3):451-61
18094028
Lab Invest. 2006 Aug;86(8):829-41
16732298
Diabetes. 2000 Feb;49(2):225-32
10868939
Dev Biol. 2004 Jul 1;271(1):144-60
15196957
Development. 2007 Feb;134(3):427-38
17185316
EMBO J. 1994 Mar 1;13(5):1145-56
7907546
Dev Biol. 2003 Jun 1;258(1):105-16
12781686
Nat Biotechnol. 2006 Dec;24(12):1481-3
17160042
Horm Metab Res. 2008 Feb;40(2):147-54
18283633
Diabetes. 2007 Apr;56(4):950-9
17229940
Dev Biol. 2004 Apr 1;268(1):174-84
15031114
Curr Biol. 2001 Sep 4;11(17):1358-63
11553330
J Clin Endocrinol Metab. 2003 Sep;88(9):4398-406
12970316
Genes Dev. 2006 Sep 1;20(17):2465-78
16951258
Dev Dyn. 2000 Aug;218(4):615-27
10906780
Dev Biol. 2005 Aug 15;284(2):399-411
16026781
Nat Rev Mol Cell Biol. 2002 Mar;3(3):187-94
11994739
Front Biosci. 2008 May 01;13:6170-82
18508651
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17438-43
17088535
Development. 2007 Jun;134(12):2207-17
17507400
Mech Dev. 2006 Jul;123(7):501-12
16822656
Mol Endocrinol. 1993 Oct;7(10):1275-83
7505393
Dev Dyn. 2005 Apr;232(4):950-7
15739227
Development. 2005 Jul;132(13):2969-80
15930104
EMBO J. 2006 Mar 22;25(6):1344-52
16511571
Transl Res. 2008 Jun;151(6):293-302
18514140
Development. 2000 Aug;127(16):3533-42
10903178
Dev Genes Evol. 2004 Sep;214(9):432-41
15322880
Genes Dev. 1998 Dec 1;12(23):3752-63
9851981
Genes Dev. 2006 Jun 1;20(11):1441-6
16751182
Diabetes Res Clin Pract. 2007 Oct;78(1):1-7
17349714