Tbx2 misexpression impairs deployment of second heart field derived progenitor cells to the arterial pole of the embryonic heart.
Tbx2 is a member of the T-box family of transcription factors that play important roles during heart development. In the embryonic heart tube, Tbx2 is expressed in non-chamber myocardium (outflow tract and interventricular canal) and has been shown to block chamber formation. We have developed a genetic system to conditionally misexpress Tbx2 in the embryonic mouse heart at early stages of development. We show that Tbx2 expression throughout the myocardium of the heart tube both represses proliferation and impairs secondary heart field (SHF) progenitor cell deployment into the outflow tract (OFT). Repression of proliferation is accompanied by the upregulation of Ndrg2 and downregulation of Ndrg4 expression, both genes believed to be involved in cell growth and proliferation. Impaired deployment of SHF cells from the pharyngeal mesoderm is accompanied by downregulation of the cell adhesion molecules Alcam and N-cadherin in the anterior part of the embryonic heart. Tbx2 misexpression also results in downregulation of Tbx20 within the OFT, indicating complex and region-specific transcriptional cross-regulation between the two T-box genes.
Dupays
Laurent
L
Division of Developmental Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
Kotecha
Surendra
S
Angst
Brigitt
B
Mohun
Timothy J
TJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C485172:Ndr2 protein, mouse; C527709:Ndrg4 protein, mouse; D009419:Nerve Tissue Proteins; D011506:Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C486013:Tbx20 protein, mouse