Disease relevance of Tbx2

• Northern blot analysis confirmed the correlation of expression of several genes, including IBP10 and osf-2, in fibroblast NIH3T3 and rat osteosarcoma ROS17/2.8 cells differentially expressing Tbx2 [1].

High impact information on Tbx2

• Our data provide a potential mechanism for chamber-restricted gene activity in which the cooperative action of Tbx2 and Nkx2.5 inhibits expression in the AVC [2].
• In the Hesr1-misexpressing heart, the boundaries of the AV canal are poorly defined, and the expression levels of specific markers of the AV myocardium, Bmp2 and Tbx2, are either very weak or undetectable [3].
• Tbx2, therefore, is envisaged to constitute a feedback loop that sharpens the border with the developing AVC and IC by delimiting Hey gene expression to within prospective chamber regions [4].
• We provide evidence that Tbx2 is a direct target for repression by Tbx20 in developing heart [5].
• We present a model whereby Tbx2 directly represses Nmyc1 in outflow tract and atrioventricular canal of the developing heart, resulting in relatively low proliferation [5].

Biological context of Tbx2

• Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development [6].
• Tbx2 is a member of the T-box transcription factor gene family, and is expressed in a variety of tissues and organs during embryogenesis [6].
• We have used targeted mutagenesis in mice to investigate Tbx2 function [6].
• 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 (dpc) [6].
• Our study supports the idea that SRF embryonic cardiac gene expression is dependent upon the SRF 3'-UTR enhancer, Tbx2, Tbx5, and TIP60 histone acetyltransferase activity [7].

Anatomical context of Tbx2

• Analysis of homozygous mutants also highlights a role for Tbx2 during hindlimb digit development [6].
• The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes [8].
• In several cases there is complementary expression of different genes in 2 interacting tissues, as in the lung epithelium (Tbx1) and lung mesenchyme (Tbx2-5), and in mammary buds (Tbx3) and mammary stroma (Tbx2) [9].
• In cell culture, Tbx3 and its close relative Tbx2 are capable of immortalizing mouse embryo fibroblasts [10].
• Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway [11].

Associations of Tbx2 with chemical compounds

• In one of these genes, T-box binding protein-2 (Tbx-2), an RA response element, was identified in the promoter region that mediates the RA responsiveness of this gene [12].

Physical interactions of Tbx2

• We have also found that Tbx2 directly binds to the Nmyc1 promoter in developing heart, and can repress expression of the Nmyc1 promoter in transient transfection studies [5].

Regulatory relationships of Tbx2

• Tbx20-null mice exhibit severely hypoplastic hearts and express Tbx2, which is normally restricted to outflow tract and atrioventricular canal, throughout the heart [5].
• Tbx2 represses expression of Connexin43 in osteoblastic-like cells [13].

Other interactions of Tbx2

• This is a clear reflection of the evolutionary relationship between the 5 genes since the divergence of Tbx1 occurred long before the relatively recent divergence of Tbx2 and 3 and Tbx4 and 5 from common ancestral genes [9].
• In mice, all of these genes have expression patterns indicative of involvement in embryonic induction (Chapman et al. (1996) Dev. Dyn., in press), and four (Tbx2-Tbx5) are represented as two cognate, linked gene pairs (Agulnik et al., (1996), Genetics, in press) [14].
• By generating an ectopic ZPA, by grafting a sonic hedgehog (SHH)-expressing cell pellet under the anterior AER, we found that Tbx2 expression can lie downstream of SHH [15].
• Interestingly, the expression of pleiotrophin (osf-1) and collagen I alpha with Tbx2 transfection showed an inverse regulatory correlation between NIH3T3 and ROS17/2.8 cells [1].

Analytical, diagnostic and therapeutic context of Tbx2

• Microarray analysis of Tbx2-directed gene expression: a possible role in osteogenesis [1].
• In an attempt to identify genes that may be regulated by Tbx2, mouse cDNA microarrays were used to analyze differential gene expression profiles, comparing stably transfected NIH3T3 cells overexpressing Tbx2 and vector-transfected controls [1].

References