High impact information on Tbx3

• Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome [1].
• Tbx-2 and Tbx-3 are expressed in anterior and posterior domains in wings and legs, as well as throughout the flank [2].
• We show that expression of Tbx3 together with Myc or oncogenic Ras (H-Ras(Val17)) leads to efficient transformation of mouse embryo fibroblasts [3].
• Mutations in Tbx3 cause ulnar-mammary syndrome, an autosomal dominant disorder characterized by upper limb defects, apocrine-gland defects including mammary hypoplasia, and tooth, hair and genital defects [3].
• Here we carried out tissue transplantations, grafted beads soaked in Shh, Bmps, and Noggin in chick limb buds, and analysed Tbx3 expression [4].

Biological context of Tbx3

• Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed [5].
• Blocking Tbx3 expression by small interfering RNA decreased cell number and [(3)H]Thymidine incorporation (P < 0.01) [6].
• In spite of a large body of evidence implicating these genes in cell cycle control through the p19(Arf)/p53 pathways, we find no evidence for involvement of these pathways either in embryonic lethality of homozygous mutants or in the mammary gland phenotype of Tbx3 heterozygous mice [7].
• However, the deficiency in maintenance of the mammary placodes in Tbx2, Tbx3 double heterozygous mice is more marked than in Tbx3 single heterozygotes, indicating a genetic interaction between the two genes [7].
• The harmonization between Tbx3 and Bmp4 therefore controls cell proliferation to regulate secondary palate development [8].

Anatomical context of Tbx3

• Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region [5].
• Tbx3 is expressed earliest, in the inner cell mass of the blastocyst [9].
• 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].
• Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos [10].
• Anterior Tbx3 expression appears to be related to the width of limb bud, which determines digit number [4].

Associations of Tbx3 with chemical compounds

• We also investigated Tbx3 expression in limb buds of chicken and mouse mutants and retinoid-deficient quail in which anteroposterior patterning is abnormal [4].

Regulatory relationships of Tbx3

• We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently [10].
• The function of Tbx3 in regulating Nppa and Cx40 promoter activity was studied in vitro [5].
• Pretreatment with TNF-alpha blocked GH-induced Tbx3 expression [6].
• Real-time RT-PCR analysis determined that pretreatment with IGF-binding protein-4 did not block GH-induced Tbx3 expression in vitro [6].
• In contrast, overexpression of Bmp4 inhibited both Tbx3 and Tbx15 expression [11].

Other interactions of Tbx3

• Tbx3 expression increased during osteoblast differentiation and following BMP-7 and Wnt3a treatment (P </= 0.05) [6].
• Tbx3 expression is reported to be associated with Bmp4 signaling during the process of organogenesis in other areas, such as limb development [8].

Analytical, diagnostic and therapeutic context of Tbx3

• In cell culture, Tbx3 and its close relative Tbx2 are capable of immortalizing mouse embryo fibroblasts [3].
• Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation [6].

References