title: Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm.
abstract: Elucidating the gene regulatory networks that govern pharyngeal arch artery (PAA) development is an important goal, as such knowledge can help to identify new genes involved in cardiovascular disease. The transcription factor Tbx1 plays a vital role in PAA development and is a major contributor to cardiovascular disease associated with DiGeorge syndrome. In this report, we used various genetic approaches to reveal part of a signalling network by which Tbx1 controls PAA development in mice. We investigated the crucial role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1. We found that PAA formation requires the pharyngeal surface ectoderm as a key signalling centre from which Gbx2, in response to Tbx1, triggers essential directional cues to the adjacent cardiac neural crest cells (cNCCs) en route to the caudal PAAs. Abrogation of this signal generates cNCC patterning defects leading to PAA abnormalities. Finally, we showed that the Slit/Robo signalling pathway is activated during cNCC migration and that components of this pathway are affected in Gbx2 and Tbx1 mutant embryos at the time of PAA development. We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development.
authors.affiliation: Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Amélie
authors.initials: A
authors.lastname: Calmont
authors.forename: Sarah
authors.initials: S
authors.lastname: Ivins
authors.forename: Kelly Lammerts
authors.initials: KL
authors.lastname: Van Bueren
authors.forename: Irinna
authors.initials: I
authors.lastname: Papangeli
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kyriakopoulou
authors.forename: William D
authors.initials: WD
authors.lastname: Andrews
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Anne M
authors.initials: AM
authors.lastname: Moon
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Illingworth
authors.forename: M Albert
authors.initials: MA
authors.lastname: Basson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
mesh_terms: D000818:Animals; D001158:Arteries / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology*; D019521:Body Patterning / Q000502:physiology*; D001934:Branchial Region / Q000002:abnormalities / Q000098:blood supply / Q000196:embryology; D002465:Cell Movement / Q000502:physiology*; D004475:Ectoderm / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D006023:Glycoproteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D020825:T-Box Domain Proteins; D000097905:Roundabout Proteins; C513182:Gbx2 protein, mouse; C491573:Tbx1 protein, mouse; C120566:slit protein, vertebrate
references.citation: Dev Cell. 2006 Jan;10(1):81-92
references.pmid: 16399080
references.citation: Development. 2008 May;135(9):1615-24
references.pmid: 18367558
references.citation: Hum Mol Genet. 2002 Apr 15;11(8):915-22
references.pmid: 11971873
references.citation: Dev Biol. 2008 Apr 15;316(2):524-37
references.pmid: 18328475
references.citation: Am J Anat. 1991 Sep;192(1):79-88
references.pmid: 1750383
references.citation: Development. 2001 Aug;128(16):3061-70
references.pmid: 11688556
references.citation: Development. 2006 Sep;133(18):3587-95
references.pmid: 16914493
references.citation: Dev Biol. 2008 Sep 1;321(1):251-62
references.pmid: 18625214
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11428-31
references.pmid: 11562466
references.citation: J Neurobiol. 1997 Jun 20;32(7):722-46
references.pmid: 9183749
references.citation: Nat Cell Biol. 2000 Feb;2(2):96-102
references.pmid: 10655589
references.citation: J Clin Invest. 2007 Feb;117(2):353-63
references.pmid: 17273555
references.citation: Nature. 2000 Sep 14;407(6801):221-6
references.pmid: 11001064
references.citation: Development. 2006 Mar;133(5):977-87
references.pmid: 16452092
references.citation: Anat Rec. 1985 Sep;213(1):87-93
references.pmid: 4073565
references.citation: Circulation. 1987 Jan;75(1):255-64
references.pmid: 3791607
references.citation: Cardiovasc Res. 1999 Oct;44(1):185-96
references.pmid: 10615402
references.citation: Semin Cell Dev Biol. 2005 Dec;16(6):683-93
references.pmid: 16043371
references.citation: Cell. 1999 Mar 19;96(6):795-806
references.pmid: 10102268
references.citation: Nature. 2001 Mar 1;410(6824):97-101
references.pmid: 11242049
references.citation: Hum Mol Genet. 2001 Apr 15;10(9):997-1002
references.pmid: 11309372
references.citation: Development. 2005 Oct;132(19):4387-95
references.pmid: 16141220
references.citation: Dev Biol. 1997 Apr 15;184(2):222-33
references.pmid: 9133432
references.citation: Dev Biol. 1999 Aug 15;212(2):290-306
references.pmid: 10433822
references.citation: Dev Biol. 2005 Aug 1;284(1):233-45
references.pmid: 15996652
references.citation: Nat Genet. 1998 Feb;18(2):136-41
references.pmid: 9462741
references.citation: Neural Dev. 2008 Nov 05;3:29
references.pmid: 18986510
references.citation: Development. 2005 Dec;132(23):5307-15
references.pmid: 16284121
references.citation: Development. 2002 Oct;129(19):4591-603
references.pmid: 12223415
references.citation: J Cell Biol. 2003 Jul 21;162(2):269-79
references.pmid: 12876276
references.citation: Science. 1984 Feb 3;223(4635):498-500
references.pmid: 6606851
references.citation: Dev Biol. 2002 Nov 1;251(1):157-66
references.pmid: 12413905
references.citation: Dev Dyn. 1995 Dec;204(4):372-82
references.pmid: 8601031
references.citation: Dev Biol. 2004 Mar 1;267(1):190-202
references.pmid: 14975726
references.citation: Hum Mol Genet. 2005 Apr 1;14(7):885-92
references.pmid: 15703190
references.citation: Development. 2004 Jul;131(14):3367-79
references.pmid: 15226254
references.citation: Development. 2004 Jul;131(13):3217-27
references.pmid: 15175244
references.citation: Mol Cell Neurosci. 2008 Apr;37(4):719-30
references.pmid: 18272390
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2475-80
references.pmid: 18250318
references.citation: Development. 2004 Nov;131(21):5491-502
references.pmid: 15469978
references.citation: Nat Med. 2003 Feb;9(2):173-82
references.pmid: 12539040
references.citation: Genes Dev. 1991 Jan;5(1):105-19
references.pmid: 1989904
references.citation: Nat Rev Genet. 2001 Nov;2(11):858-68
references.pmid: 11715041
references.citation: J Neurosci. 1998 Jan 1;18(1):237-50
references.pmid: 9412504
references.citation: Development. 2003 Dec;130(25):6361-74
references.pmid: 14623825
references.citation: Dev Biol. 2007 Feb 15;302(2):670-82
references.pmid: 17074316
references.citation: Dev Biol. 2005 Jun 15;282(2):411-21
references.pmid: 15950606
references.citation: Mol Cell Neurosci. 2005 Dec;30(4):485-93
references.pmid: 16226035
references.citation: Development. 1999 Nov;126(21):4827-38
references.pmid: 10518499
references.citation: Dev Biol. 2008 Jan 15;313(2):648-58
references.pmid: 18054781
references.citation: Dev Dyn. 1996 Aug;206(4):379-90
references.pmid: 8853987
references.citation: Dev Biol. 2003 Sep 1;261(1):251-67
references.pmid: 12941633
references.citation: Dev Biol. 2001 Jul 1;235(1):62-73
references.pmid: 11412027
references.citation: Hum Mol Genet. 2006 Dec 1;15(23):3394-410
references.pmid: 17047027
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: J Comp Neurol. 2004 Jan 19;468(4):467-81
references.pmid: 14689480
references.citation: Anat Rec. 1993 Feb;235(2):261-74
references.pmid: 8420394
references.citation: Circ Res. 1995 Aug;77(2):211-5
references.pmid: 7614707
references.citation: Dev Dyn. 2006 Sep;235(9):2592-602
references.pmid: 16881058
references.citation: Development. 1997 Aug;124(15):2923-34
references.pmid: 9247335
references.citation: Development. 2000 Apr;127(8):1607-16
references.pmid: 10725237
references.citation: Hum Mol Genet. 2008 Jan 1;17(1):150-7
references.pmid: 17916582
references.citation: Nat Genet. 2001 Mar;27(3):286-91
references.pmid: 11242110
references.citation: FASEB J. 2009 Feb;23(2):513-22
references.pmid: 18948384
references.citation: J Embryol Exp Morphol. 1975 Aug;34(1):125-54
references.pmid: 1185098
references.citation: Nat Med. 2008 Apr;14(4):448-53
references.pmid: 18345009
references.citation: Dev Biol. 2005 Sep 15;285(2):554-69
references.pmid: 16109395
references.citation: Cell. 2001 Feb 23;104(4):619-29
references.pmid: 11239417
references.citation: Development. 2001 Aug;128(16):3071-80
references.pmid: 11688557
references.citation: Development. 1995 Feb;121(2):439-51
references.pmid: 7768185
references.citation: Genes Dev. 2003 Jan 15;17(2):269-81
references.pmid: 12533514
references.citation: Nucleic Acids Res. 2003 Jul 15;31(14):e73
references.pmid: 12853650
references.citation: Development. 2008 May;135(9):1605-13
references.pmid: 18356247
references.citation: Nature. 1999 Sep 23;401(6751):379-83
references.pmid: 10517636
references.citation: Neuron. 2002 Jan 17;33(2):219-32
references.pmid: 11804570
references.citation: Lancet. 2003 Oct 25;362(9393):1366-73
references.pmid: 14585638
references.citation: Development. 2002 Oct;129(19):4605-11
references.pmid: 12223416
references.citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7729-34
references.pmid: 16684884
references.citation: Neuron. 2002 Sep 26;36(1):31-43
references.pmid: 12367504