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Status |
Public on Aug 01, 2014 |
Title |
Tbx2 and Tbx3 impose nodal phenotype and induce cushion formation in the atrioventricular canal |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Rationale: A critical step in heart development is the coordinated formation of nodal myocardium and cushion tissue from the atrioventricular canal (AVC). After its specification, the myocardium of the AVC aligns the chambers, forms the AV node, and induces the formation of the mesenchymal AV cushions, primordia of valves and septa, while it resists working myocardial differentiation.
Objective: To assess what roles Tbx2 and Tbx3, two closely related T-box transcription factors expressed in the AVC, play in these processes.
Methods and Results: We analyzed mice ectopically expressing Tbx3 in the atrial myocardium by genome-wide microarray and expression analysis. We found a prominent role for Tbx3 in defining the nodal phenotype by repressing working myocardial genes (sarcomeric, mitochondrial, fast conduction) and cell proliferation regulators, and in inducing node-associated genes. Moreover, there was a striking induction of genes associated with endocardial cushions and mesenchyme. Using gain-of-function models, we found that in the developing heart both Tbx2 and Tbx3 induce ectopic Bmp2 and Tgfb2 expression and endocardial cushion formation. Analysis of compound Tbx2/Tbx3 mutant embryos revealed that upon loss of more than two functional alleles, expansion of the AV myocardium does not occur and AV cushions fail to form.
Conclusions: Tbx2 and Tbx3 locally stimulate development of the AVC myocardium, induce the AV nodal phenotype therein and trigger AV cushion formation from the overlying AV endocardium, providing a mechanism for the colocalization and coordination of these two important processes in heart development.
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Overall design |
Nppa-Cre4 (Cre4) mice were crossed with CT mice to obtain efficient activation of Tbx3 in atria of double transgenic Cre4-CT mice, as previously described (Hoogaars et al., 2007). To investigate the gene expression profile of atria of Cre4-CT mice, we performed whole genome microarray analysis using Sentrix Mouse-6 oligonucleotide beadchips.
We compared the atrial gene expression profiles of six male double transgenic Cre4-CT mice and six male Cre4 control mice.
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Contributor(s) |
Hoogaars WM, Buermans HP, Clout DE, Moorman AF, 't Hoen PA, Christoffels VM |
Citation missing |
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Submission date |
Jan 30, 2008 |
Last update date |
Aug 01, 2014 |
Contact name |
Henk Buermans |
E-mail(s) |
h.buermans@lumc.nl
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Phone |
+31715268558
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Organization name |
Leiden University Medical Center
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Department |
Human Genetics
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Lab |
Leiden Genome Technology Center
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Street address |
Albinusdreef 2
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City |
Leiden |
State/province |
ZH |
ZIP/Postal code |
2300 RC |
Country |
Netherlands |
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Platforms (1) |
GPL4234 |
Sentrix Mouse-6 Expression BeadChip |
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Samples (12)
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Relations |
BioProject |
PRJNA108551 |
Supplementary data files not provided |
Processed data included within Sample table |
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