Tbx6,a Mouse T-Box Gene Implicated in Paraxial Mesoderm Formation at Gastrulation

AbstractThe T-box genes constitute an evolutionarily conserved family of putative transcription factors which are expressed in discrete domains during embryogenesis, suggesting that they may play roles in inductive interactions. Members have been identified by virtue of their homology to the prototypical T-box gene,TorBrachyury,which is required for mesoderm formation and axial elongation during embryogenesis. We have previously reported the discovery of six new mouse T-box genes,Tbx1–Tbx6,and described the expression patterns ofTbx1–Tbx5(Bollaget al.,1994; Agulniket al.,1996; Chapmanet al.,1996; Gibson-Brownet al.,1996). 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 ofTbx6transcripts during embryogenesis. The gene codes for a 1.9-kb transcript with an open reading frame coding for a 540-amino acid protein, with a predicted molecular weight of 59 kDa.Tbx6maps to chromosome 7 and does not appear to be linked to any known mutation. Unlike other members of the mouse T-box gene family which are expressed in a wide variety of tissues derived from all germ layers,Tbx6expression is quite restricted.Tbx6transcripts are first detected in the gastrulation stage embryo in the primitive streak and newly recruited paraxial mesoderm. Later in development,Tbx6expression is restricted to presomitic, paraxial mesoderm and to the tail bud, which replaces the streak as the source of mesoderm. Expression in the tail bud persists until 12.5 days postcoitus.Tbx6expression thus overlaps that ofBrachyuryin the primitive streak and tail bud, althoughBrachyuryis expressed earlier in the primitive streak.Brachyuryis also expressed in a second domain, the node and notochord, that is not shared withTbx6.The onset ofTbx6expression is not affected in homozygous nullBrachyurymutant embryos at 7.5 days postcoitus. However,Tbx6expression is extinguished in mutant embryos as soon as theBrachyuryphenotype becomes evident at 8.5 days postcoitus, indicating that the continued expression ofTbx6is directly or indirectly dependent uponBrachyuryexpression