title: Twist1 controls a cell-specification switch governing cell fate decisions within the cardiac neural crest.
abstract: Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages.
authors.affiliation: Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Division of Pediatrics Cardiology, Departments of Anatomy, Indiana University Medical School, Indianapolis, Indiana, United States of America.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Vincentz
authors.forename: Beth A
authors.initials: BA
authors.lastname: Firulli
authors.forename: Andrea
authors.initials: A
authors.lastname: Lin
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Spicer
authors.forename: Marthe J
authors.initials: MJ
authors.lastname: Howard
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Firulli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004475:Ectoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D055757:SOXE Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D009687:Nuclear Proteins; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse
references.citation: Nat Cell Biol. 2009 Aug;11(8):943-50
references.pmid: 19597490
references.citation: J Neurosci. 2012 Feb 8;32(6):2110-20
references.pmid: 22323723
references.citation: Am J Med Genet A. 2010 Dec;152A(12):2984-94
references.pmid: 20734335
references.citation: Dev Dyn. 2008 Dec;237(12):3809-19
references.pmid: 19035347
references.citation: Dev Biol. 2007 Jul 1;307(1):114-26
references.pmid: 17531968
references.citation: Cell Res. 2012 Jan;22(1):90-106
references.pmid: 21876555
references.citation: Development. 2000 Apr;127(8):1607-16
references.pmid: 10725237
references.citation: Neuron. 2003 Apr 10;38(1):17-31
references.pmid: 12691661
references.citation: Dev Biol. 1995 Aug;170(2):664-78
references.pmid: 7649392
references.citation: Nat Genet. 1998 Mar;18(3):266-70
references.pmid: 9500550
references.citation: Development. 2005 Jan;132(1):189-201
references.pmid: 15576406
references.citation: Development. 2000 Sep;127(18):4073-81
references.pmid: 10952904
references.citation: Annu Rev Physiol. 1998;60:267-86
references.pmid: 9558464
references.citation: Dev Biol. 2008 Aug 1;320(1):131-9
references.pmid: 18539270
references.citation: Ann Surg Oncol. 2009 Jul;16(7):1997-2005
references.pmid: 19412634
references.citation: Mol Cell Neurosci. 2004 Mar;25(3):374-82
references.pmid: 15033166
references.citation: Circ Res. 2011 Apr 15;108(8):940-9
references.pmid: 21350214
references.citation: Curr Top Dev Biol. 2010;90:1-41
references.pmid: 20691846
references.citation: Nat Genet. 2005 Apr;37(4):373-81
references.pmid: 15735646
references.citation: Genetics. 2005 Jun;170(2):971-4
references.pmid: 15802514
references.citation: Dev Biol. 2002 Jul 15;247(2):251-70
references.pmid: 12086465
references.citation: Dev Biol. 2003 Jul 1;259(1):176-87
references.pmid: 12812797
references.citation: Genesis. 2007 Sep;45(9):588-92
references.pmid: 17868088
references.citation: Genes Dev. 1995 Mar 15;9(6):686-99
references.pmid: 7729687
references.citation: Exp Cell Res. 1995 Jun;218(2):405-17
references.pmid: 7796877
references.citation: Ann N Y Acad Sci. 2010 Feb;1188:184-90
references.pmid: 20201902
references.citation: Development. 2004 Oct;131(19):4775-86
references.pmid: 15329349
references.citation: Dev Dyn. 2006 May;235(5):1345-57
references.pmid: 16502419
references.citation: Oncogene. 2010 Jun 3;29(22):3173-84
references.pmid: 20383196
references.citation: Eur J Neurosci. 2004 Jul;20(2):353-62
references.pmid: 15233745
references.citation: Dev Biol. 2003 Oct 1;262(1):183-93
references.pmid: 14512028
references.citation: J Biol Chem. 2012 Jun 15;287(25):21082-92
references.pmid: 22532563
references.citation: PLoS One. 2011;6(12):e29758
references.pmid: 22242143
references.citation: Nature. 1996 Apr 25;380(6576):711-4
references.pmid: 8614465
references.citation: Dev Biol. 1999 Nov 1;215(1):62-77
references.pmid: 10525350
references.citation: Mech Dev. 2003 Sep;120(9):1021-32
references.pmid: 14550531
references.citation: Semin Cell Dev Biol. 2007 Feb;18(1):101-10
references.pmid: 17224285
references.citation: Genes Dev. 1991 Sep;5(9):1568-76
references.pmid: 1884999
references.citation: Int J Dev Biol. 2009;53(7):909-24
references.pmid: 19378251
references.citation: Mol Cell Biol. 1997 Nov;17(11):6563-73
references.pmid: 9343420
references.citation: Dev Biol. 1989 Aug;134(2):402-12
references.pmid: 2744240
references.citation: Adv Exp Med Biol. 2006;589:134-54
references.pmid: 17076279
references.citation: J Immunol. 2012 Jul 15;189(2):832-40
references.pmid: 22685315
references.citation: Dev Biol. 1999 Aug 1;212(1):191-203
references.pmid: 10419695
references.citation: Mech Dev. 2002 Sep;117(1-2):115-22
references.pmid: 12204252
references.citation: Dev Cell. 2005 Feb;8(2):179-92
references.pmid: 15691760
references.citation: Nucleic Acids Res. 1999 Mar 15;27(6):1409-20
references.pmid: 10037800
references.citation: Hum Mol Genet. 1997 Aug;6(8):1369-73
references.pmid: 9259286
references.citation: Cancer Cell. 2004 Dec;6(6):625-30
references.pmid: 15607966
references.citation: Science. 1983 Jun 3;220(4601):1059-61
references.pmid: 6844926
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: Dev Dyn. 2010 Nov;239(11):3086-97
references.pmid: 20882677
references.citation: Dev Biol. 2005 Jan 15;277(2):271-86
references.pmid: 15617674
references.citation: Cell. 2004 Jun 25;117(7):927-39
references.pmid: 15210113
references.citation: Mech Dev. 2009 Jan-Feb;126(1-2):80-9
references.pmid: 18955134
references.citation: Dev Cell. 2004 Mar;6(3):423-35
references.pmid: 15030764
references.citation: J Biol Chem. 2007 Sep 14;282(37):27536-27546
references.pmid: 17652084
references.citation: Development. 2001 Aug;128(16):3071-80
references.pmid: 11688557
references.citation: FEBS Lett. 2001 Mar 9;492(1-2):112-8
references.pmid: 11248247
references.citation: Development. 2010 Mar;137(5):775-84
references.pmid: 20147379
references.citation: Dev Biol. 2008 Jul 15;319(2):179-91
references.pmid: 18501887
references.citation: FASEB J. 1994 Jul;8(10):699-706
references.pmid: 8050668
references.citation: Mol Cell Biol. 2004 Aug;24(15):6635-44
references.pmid: 15254231
references.citation: Am J Hum Genet. 1998 Jun;62(6):1370-80
references.pmid: 9585583
references.citation: Development. 2001 Aug;128(16):3061-70
references.pmid: 11688556
references.citation: Nucleic Acids Res. 2009 Jun;37(11):3689-98
references.pmid: 19372275
references.citation: Nature. 1999 May 27;399(6734):366-70
references.pmid: 10360575
references.citation: J Anat. 2008 Jan;212(1):1-11
references.pmid: 18031480
references.citation: Development. 2006 Oct;133(20):4015-24
references.pmid: 17008447
references.citation: Dev Biol. 2002 Jan 1;241(1):106-16
references.pmid: 11784098
references.citation: Mol Cell Neurosci. 2001 Oct;18(4):394-406
references.pmid: 11640896
references.citation: Development. 1999 Sep;126(18):4087-94
references.pmid: 10457017
references.citation: Nucleic Acids Res. 1993 Aug 25;21(17):3951-7
references.pmid: 8371971