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PMID: 15634698 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis.

Development (Cambridge, England) ·Vol. 132 ·No. 3 ·2005-02-00 ·Pages 553-63

Brown DD, Martz SN, Binder O, Goetz SC, Price BM, Smith JC, Conlon FL

Abstract

Members of the T-box family of proteins play a fundamental role in patterning the developing vertebrate heart; however, the precise cellular requirements for any one family member and the mechanism by which individual T-box genes function remains largely unknown. In this study, we have investigated the cellular and molecular relationship between two T-box genes, Tbx5 and Tbx20. We demonstrate that blocking Tbx5 or Tbx20 produces phenotypes that display a high degree of similarity, as judged by overall gross morphology, molecular marker analysis and cardiac physiology, implying that the two genes are required for and have non-redundant functions in early heart development. In addition, we demonstrate that although co-expressed, Tbx5 and Tbx20 are not dependent on the expression of one another, but rather have a synergistic role during early heart development. Consistent with this proposal, we show that TBX5 and TBX20 can physically interact and map the interaction domains, and we show a cellular interaction for the two proteins in cardiac development, thus providing the first evidence for direct interaction between members of the T-box gene family.

MeSH Terms
Animals Cell Count Cell Line Cell Nucleus/metabolism Embryo, Nonmammalian/embryology,metabolism Gene Expression Regulation, Developmental Heart/embryology Humans Mice Morphogenesis Myocardium/cytology,metabolism Protein Binding T-Box Domain Proteins/genetics,metabolism Transcription, Genetic/genetics Xenopus laevis/embryology,genetics,metabolism
Chemicals
T-Box Domain Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Brown Daniel D
Department of Genetics, Fordham Hall, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Martz Shauna N
Binder Olav
Goetz Sarah C
Price Brenda M J
Smith Jim C
Conlon Frank L
References (52)
52 references, click to expand
  1. Developmental expression of the Xenopus laevis Tbx20 orthologue.
    Dev Genes Evol. 2003 Jan;212(12):604-7 PMID: 12536325
  2. HrT is required for cardiovascular development in zebrafish.
    Development. 2002 Nov;129(21):5093-101 PMID: 12397116
  3. T-box genes in human disorders.
    Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R37-44 PMID: 12668595
  4. T-box genes and cardiac development.
    Birth Defects Res C Embryo Today. 2003 Feb;69(1):25-37 PMID: 12768655
  5. Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations with atrial septal defect and hypoplastic left heart syndrome.
    J Am Coll Cardiol. 2003 Jun 4;41(11):2072-6 PMID: 12798584
  6. Evolution of Brachyury proteins: identification of a novel regulatory domain conserved within Bilateria.
    Dev Biol. 2003 Aug 15;260(2):352-61 PMID: 12921737
  7. TBX5 nuclear localization is mediated by dual cooperative intramolecular signals.
    J Mol Cell Cardiol. 2003 Oct;35(10):1191-5 PMID: 14519429
  8. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart.
    Dev Biol. 2003 Oct 15;262(2):206-24 PMID: 14550786
  9. Role of TBX1 in human del22q11.2 syndrome.
    Lancet. 2003 Oct 25;362(9393):1366-73 PMID: 14585638
  10. T-box genes in early embryogenesis.
    Dev Dyn. 2004 Jan;229(1):201-18 PMID: 14699590
  11. Identification of the TBX5 transactivating domain and the nuclear localization signal.
    Gene. 2004 Apr 14;330:9-18 PMID: 15087119
  12. DiGeorge syndrome: an update.
    Curr Opin Cardiol. 2004 May;19(3):201-4 PMID: 15096950
  13. Differential expression and function of Tbx5 and Tbx20 in cardiac development.
    J Biol Chem. 2004 Apr 30;279(18):19026-34 PMID: 14978031
  14. Tbx12 regulates eye development in Xenopus embryos.
    Biochem Biophys Res Commun. 2004 May 28;318(2):485-9 PMID: 15120626
  15. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system.
    Development. 2004 Aug;131(16):4107-16 PMID: 15289437
  16. In situ hybridization: an improved whole-mount method for Xenopus embryos.
    Methods Cell Biol. 1991;36:685-95 PMID: 1811161
  17. XNkx-2.5, a Xenopus gene related to Nkx-2.5 and tinman: evidence for a conserved role in cardiac development.
    Dev Biol. 1994 Mar;162(1):325-8 PMID: 7545912
  18. Induction of cardiac muscle differentiation in isolated animal pole explants of Xenopus laevis embryos.
    Development. 1993 Jul;118(3):865-75 PMID: 8076523
  19. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut.
    J Biol Chem. 1994 Sep 16;269(37):23177-84 PMID: 8083222
  20. Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis.
    Dev Biol. 1994 Oct;165(2):432-41 PMID: 7958411
  21. Toward a molecular understanding of congenital heart disease.
    Circulation. 1995 Jan 15;91(2):494-504 PMID: 7805255
  22. Incidence of congenital heart disease: I. Postnatal incidence.
    Pediatr Cardiol. 1995 May-Jun;16(3):103-13 PMID: 7617503
  23. Induction of epidermis and inhibition of neural fate by Bmp-4.
    Nature. 1995 Jul 27;376(6538):331-3 PMID: 7630398
  24. Incidence of congenital heart disease: II. Prenatal incidence.
    Pediatr Cardiol. 1995 Jul-Aug;16(4):155-65 PMID: 7567659
  25. Holt-Oram syndrome: a clinical genetic study.
    J Med Genet. 1996 Apr;33(4):300-7 PMID: 8730285
  26. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development.
    Dev Dyn. 1996 Aug;206(4):379-90 PMID: 8853987
  27. New understandings in the genetics of congenital heart disease.
    Curr Opin Pediatr. 1996 Oct;8(5):505-11 PMID: 8946132
  28. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.
    Nat Genet. 1997 Jan;15(1):21-9 PMID: 8988164
  29. Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome.
    Nat Genet. 1997 Jan;15(1):30-5 PMID: 8988165
  30. A vegetally localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation.
    Development. 1997 May;124(9):1689-98 PMID: 9165117
  31. Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.
    Genomics. 1997 Aug 1;43(3):267-77 PMID: 9268629
  32. Regulation in the heart field of zebrafish.
    Development. 1998 Mar;125(6):1095-101 PMID: 9463356
  33. Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2919-24 PMID: 10077612
  34. Tbx5 is essential for heart development.
    Development. 1999 Apr;126(8):1739-51 PMID: 10079235
  35. Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome.
    J Biol Chem. 2003 Mar 7;278(10):8780-5 PMID: 12499378
  36. Early signals in cardiac development.
    Circ Res. 2002 Sep 20;91(6):457-69 PMID: 12242263
  37. Tbx5 and the retinotectum projection.
    Science. 2000 Jan 7;287(5450):134-7 PMID: 10615048
  38. Confocal imaging of early heart development in Xenopus laevis.
    Dev Biol. 2000 Feb 1;218(1):64-73 PMID: 10644411
  39. Pax6 interacts with cVax and Tbx5 to establish the dorsoventral boundary of the developing eye.
    J Biol Chem. 2004 Nov 5;279(45):47272-7 PMID: 15322073
  40. The morphology of heart development in Xenopus laevis.
    Dev Biol. 2000 Feb 1;218(1):74-88 PMID: 10644412
  41. Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach.
    Dev Biol. 2000 Jun 1;222(1):124-34 PMID: 10885751
  42. Expression of atrial natriuretic factor (ANF) during Xenopus cardiac development.
    Dev Genes Evol. 2000 Dec;210(12):638-40 PMID: 11151301
  43. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice.
    Nature. 2001 Mar 1;410(6824):97-101 PMID: 11242049
  44. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.
    Nat Genet. 2001 Mar;27(3):286-91 PMID: 11242110
  45. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.
    Cell. 2001 Feb 23;104(4):619-29 PMID: 11239417
  46. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation.
    Nat Genet. 2001 Jul;28(3):276-80 PMID: 11431700
  47. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease.
    Cell. 2001 Sep 21;106(6):709-21 PMID: 11572777
  48. NKX2.5 mutations in patients with tetralogy of fallot.
    Circulation. 2001 Nov 20;104(21):2565-8 PMID: 11714651
  49. Control of cardiac development by an evolutionarily conserved transcriptional network.
    Dev Biol. 2002 Jun 1;246(1):14-28 PMID: 12027431
  50. Patterning the vertebrate heart.
    Nat Rev Genet. 2002 Jul;3(7):544-56 PMID: 12094232
  51. Developmental paradigms in heart disease: insights from tinman.
    Ann Med. 2002;34(3):148-56 PMID: 12173684
  52. The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.
    Development. 2002 Oct;129(19):4635-45 PMID: 12223419
Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
Published
2005-02-00
Epub
2005-00-05
Pages
553-63
Language
English
Region
England
NLM ID
8701744
PMCID
PMC1635804
Subset
IM
Grants
NHLBI NIH HHS · R01 HL075256 · United States
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