Tbx18 and Tbx15 null-like phenotypes in mouse embryos expressing Tbx6 in somitic and lateral plate mesoderm

Abstract

Members of the T-box family of transcription factors play essential roles in cell type specification, differentiation, and proliferation during embryonic development. All T-box family members share a common DNA binding domain - the T-domain - and can therefore recognize similar sequences. Consequently, T-box proteins that are co-expressed during development have the potential to compete for binding at downstream targets. In the mouse, Tbx6 is expressed in the primitive streak and presomitic mesoderm, and is sharply down-regulated upon segmentation of the paraxial mesoderm. We sought to determine the phenotypic and molecular consequences of ectopically expressing Tbx6 within the segmented paraxial mesoderm and its derivatives using a 3-component transgenic system. The vertebral column, ribs, and appendicular skeleton were all affected in these embryos, which resembled Tbx18 and Tbx15 null embryos. We hypothesize that these phenotypes result from competition between the ectopically expressed Tbx6 and the endogenously expressed Tbx18 and Tbx15 at the binding sites of target genes. In vitro luciferase transcriptional assays provide further support for this hypothesis.

Osteoporosis- and obesity-risk interrelationships: An epigenetic analysis of GWAS-derived SNPs at the developmental geneTBX15

“…Remarkably, our analysis of eBMD GWAS data (64) indicates that the TBX18 gene is also associated with eBMD. This is consistent with the partial overlap of functions and high amino acid sequence homology between TBX15 and TBX18 proteins (26,65).…”

“…The more selective nature of the index/proxy set of SNPs might be a result of the GWAS Catalog extracting the most significant SNP from each independent locus to assign index SNPs (16). We found that 38% (36) and 51% (19) of the obesity and eBMD index/proxy SNPs as well as 15% (65) and 10% (46) of the obesity and eBMD imputed SNPs in the TBX15/WARS2 region overlapped enhancer/promoter chromatin preferentially in SAT or ostb, respectively ( Fig. 2B and F; Supplementary Material, Tables S4 -S6).…”

Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation

“…Combinatorial expression of these factors defines nascent paraxial mesoderm (T phenotype, as they all display a loss of posterior somites and PSM (Fujimoto and Yanagisawa, 1979;Chapman and Papaioannou, 1998;. However, gain-of-function studies on Tbx6 in mice (Wehn and Chapman, 2010) and T in embryonic stem cells (ESCs) (Lindsley et al, 2008) do not reveal strong mesoderm-inducing activity, raising the question as to what is the major positive regulator(s) of PSM fate.…”

The Genetic Origin of Short Tail in Endangered Korean Dog, DongGyeongi

“…TBX6 of the TBX family was found to participate in differentiation of posterior stem cells during embryo development 7 . The absence of TBX6 was reported to induce neural plate and somite development 8 , 9 . This implies that TBX6 regulates differentiation of posterior stem cells which form a tail in the later stages.…”