Disease relevance of Tbx6

• The similarity in the phenotypes we describe here and that of some human birth defects, such as spondylocostal dysostosis, raises the possibility that mutations in Tbx6 or components of this pathway may be responsible for these defects [1].

High impact information on Tbx6

• Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6 [2].
• We now report the creation of a mutation in Tbx6 that profoundly affects the differentiation of paraxial mesoderm [2].
• The embryonic pattern of expression of Tbx6 in somite precursor cells suggests that this gene may be involved in the specification of paraxial mesoderm [2].
• Embryos lacking the T-box-containing transcription factors, Brachyury or Tbx6, also lack paraxial mesoderm [3].
• Tbx6 expression thus overlaps that of Brachyury in the primitive streak and tail bud, although Brachyury is expressed earlier in the primitive streak [4].

Biological context of Tbx6

• Tbx6 maps to chromosome 7 and does not appear to be linked to any known mutation [4].
• We have obtained cDNA clones encoding the full-length Tbx6 protein from screens of gastrulation-stage mouse cDNA libraries and determined the spatial and temporal distribution of Tbx6 transcripts during embryogenesis [4].
• As a first step toward identifying downstream targets of Tbx6, we examined the DNA binding properties of Tbx6 and identified a Tbx6 consensus binding site [5].
• We have begun to investigate how Tbx6 expression is controlled during development using a transgenic approach to identify the cis-acting regulatory regions [6].
• By fine genetic mapping and complementation testing we have identified Tbx6, a gene essential for paraxial mesoderm formation, as the gene mutated in rv [7].

Anatomical context of Tbx6

• Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at gastrulation [4].
• Tbx6 transcripts are first detected in the gastrulation stage embryo in the primitive streak and newly recruited paraxial mesoderm [4].
• Brachyury is also expressed in a second domain, the node and notochord, that is not shared with Tbx6 [4].
• Unlike other members of the mouse T-box gene family which are expressed in a wide variety of tissues derived from all germ layers, Tbx6 expression is quite restricted [4].
• Defective somite patterning in mouse embryos with reduced levels of Tbx6 [1].

Associations of Tbx6 with chemical compounds

• Tbx6 is a member of the T-box family of proteins, which share a region of homology corresponding to the DNA-binding domain of the transcription factor T [8].

Physical interactions of Tbx6

• We uncovered four putative Tbx6 binding sites within a Dll1 paraxial mesoderm enhancer and show that Tbx6 can bind two of these sites in vitro [5].

Other interactions of Tbx6

• The onset of Tbx6 expression is not affected in homozygous null Brachyury mutant embryos at 7.5 days postcoitus [4].
• Dll1 is a downstream target of Tbx6 in the paraxial mesoderm [5].
• In our current study, we show that a T-box transcription factor, Tbx6, is essential for Mesp2 expression [9].
• Furthermore, we show that FGFR1 functions in mesoderm cell fate specification by positively regulating Brachyury and Tbx6 expression [10].
• Regulation of Tbx6 expression by Notch signaling [6].

Analytical, diagnostic and therapeutic context of Tbx6

• To discover whether different T-box proteins interact on the same down stream targets in areas of expression overlap, we have explored potential interactions between Tbx6 and T (Brachyury) in genetic crosses [11].

References