Chapman D L, Agulnik I, Hancock S, Silver L M, Papaioannou V E
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, New York, 10032, USA.
Dev Biol. 1996 Dec 15;180(2):534-42. doi: 10.1006/dbio.1996.0326.
The 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, T or Brachyury, 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 of Tbx1-Tbx5 (Bollag et al., 1994; Agulnik et al., 1996; Chapman et al., 1996; Gibson-Brown et 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 of Tbx6 transcripts 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. Tbx6 maps 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, Tbx6 expression is quite restricted. Tbx6 transcripts are first detected in the gastrulation stage embryo in the primitive streak and newly recruited paraxial mesoderm. Later in development, Tbx6 expression 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. Tbx6 expression thus overlaps that of Brachyury in the primitive streak and tail bud, although Brachyury is expressed earlier in the primitive streak. Brachyury is also expressed in a second domain, the node and notochord, that is not shared with Tbx6. The onset of Tbx6 expression is not affected in homozygous null Brachyury mutant embryos at 7.5 days postcoitus. However, Tbx6 expression is extinguished in mutant embryos as soon as the Brachyury phenotype becomes evident at 8.5 days postcoitus, indicating that the continued expression of Tbx6 is directly or indirectly dependent upon Brachyury expression.
T-box基因构成了一个在进化上保守的假定转录因子家族，它们在胚胎发育过程中于离散区域表达，这表明它们可能在诱导性相互作用中发挥作用。通过与原型T-box基因T（或Brachyury）的同源性鉴定出了该家族的成员，T（或Brachyury）基因在胚胎发育过程中对于中胚层形成和轴向伸长是必需的。我们之前报道了六个新的小鼠T-box基因Tbx1 - Tbx6的发现，并描述了Tbx1 - Tbx5的表达模式（博拉格等人，1994年；阿古尼克等人，1996年；查普曼等人，1996年；吉布森 - 布朗等人，1996年）。我们从原肠胚形成阶段的小鼠cDNA文库筛选中获得了编码全长Tbx6蛋白的cDNA克隆，并确定了胚胎发育过程中Tbx6转录本的时空分布。该基因编码一个1.9 kb的转录本，其开放阅读框编码一个540个氨基酸的蛋白质，预测分子量为59 kDa。Tbx6定位于7号染色体，似乎与任何已知突变均无关联。与小鼠T-box基因家族的其他成员不同，后者在源自所有三个胚层的多种组织中表达，而Tbx6的表达相当局限。Tbx6转录本首先在原肠胚形成阶段的胚胎中于原条和新募集的近轴中胚层中被检测到。在发育后期，Tbx6的表达局限于前体节、近轴中胚层以及尾芽，尾芽取代原条成为中胚层的来源。在尾芽中的表达一直持续到交配后12.5天。因此，Tbx6在原条和尾芽中的表达与Brachyury的表达重叠，尽管Brachyury在原条中表达得更早。Brachyury还在第二个区域即节点和脊索中表达，这一区域Tbx6并不共享。在交配后7.5天，纯合缺失Brachyury突变胚胎中Tbx6表达的起始不受影响。然而，一旦在交配后8.5天Brachyury表型变得明显，Tbx6在突变胚胎中的表达就会消失，这表明Tbx6的持续表达直接或间接依赖于Brachyury的表达。
