Tbx2 is essential for patterning the atrioventricular canal and for morphogenensis of the outflow tract during heart development

Zachary Harrelson, Robert G. Kelly, Sarah N. Goldin, Jeremy J. Gibson-Brown, Roni J. Bollag, Lee M. Silver, Virginia E. Papaioannou

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Tbx2 is a member of the T-box transcription factor gene family, and is expressed in a variety of tissues and organs during embryogenesis. In the developing heart, Tbx2 is expressed in the outflow tract, inner curvature, atrioventricular canal and inflow tract, corresponding to a myocardial zone that is excluded from chamber differentiation at 9.5 days post coitus (dpe). We have used targeted mutagenesis in mice to investigate Tbx2 function. Mice heterozygous for a Tbx2 null mutation appear normal but homozygous embryos reveal a crucial role for Tbx2 during cardiac development. Morphological defects are observed in development of the atrioventricular canal and septation of the outflow tract. Molecular analysis reveals that Tbx2 is required to repress chamber differentiation in the atrioventricular canal at 9.5 dpc. Analysis of homozygous mutants also highlights a role for Tbx2 during hindlimh digit development. Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in increased levels of p19ARF, p161NK4a, p15INK4b or p2l expression in vivo, nor is there evidence for a genetic interaction between Tbx2 and P53.

Original languageEnglish (US)
Pages (from-to)5041-5052
Number of pages12
JournalDevelopment
Volume131
Issue number20
DOIs
StatePublished - Oct 1 2004

Fingerprint

cdc Genes
Coitus
Cell Cycle Checkpoints
Mutagenesis
Embryonic Development
Cultured Cells
Transcription Factors
Embryonic Structures
Mutation
Genes

Keywords

  • Atrioventricular canal
  • Cell cycle
  • Heart development
  • Outflow tract
  • T-box
  • Tbx2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Harrelson, Z., Kelly, R. G., Goldin, S. N., Gibson-Brown, J. J., Bollag, R. J., Silver, L. M., & Papaioannou, V. E. (2004). Tbx2 is essential for patterning the atrioventricular canal and for morphogenensis of the outflow tract during heart development. Development, 131(20), 5041-5052. https://doi.org/10.1242/dev.01378

Tbx2 is essential for patterning the atrioventricular canal and for morphogenensis of the outflow tract during heart development. / Harrelson, Zachary; Kelly, Robert G.; Goldin, Sarah N.; Gibson-Brown, Jeremy J.; Bollag, Roni J.; Silver, Lee M.; Papaioannou, Virginia E.

In: Development, Vol. 131, No. 20, 01.10.2004, p. 5041-5052.

Research output: Contribution to journalArticle

Harrelson, Z, Kelly, RG, Goldin, SN, Gibson-Brown, JJ, Bollag, RJ, Silver, LM & Papaioannou, VE 2004, 'Tbx2 is essential for patterning the atrioventricular canal and for morphogenensis of the outflow tract during heart development', Development, vol. 131, no. 20, pp. 5041-5052. https://doi.org/10.1242/dev.01378
Harrelson, Zachary ; Kelly, Robert G. ; Goldin, Sarah N. ; Gibson-Brown, Jeremy J. ; Bollag, Roni J. ; Silver, Lee M. ; Papaioannou, Virginia E. / Tbx2 is essential for patterning the atrioventricular canal and for morphogenensis of the outflow tract during heart development. In: Development. 2004 ; Vol. 131, No. 20. pp. 5041-5052.
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