Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation

Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation
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DOI:
10.1006/dbio.1996.0326
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发表时间:
1996-12-15
影响因子:
2.7
通讯作者:
Papaioannou, VE
Papaioannou, VE
中科院分区:
生物学3区
文献类型:
--
作者:
Chapman, DL;Agulnik, I;Papaioannou, VE

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T-box基因构成了一个进化上保守的转录因子家族,这些转录因子在胚胎发生过程中在离散域表达,这表明它们可能在诱导相互作用中发挥作用。这些成员与典型的T-box基因T或Brachyury具有同源性,这是胚胎发生过程中中胚层形成和轴向伸长所必需的。我们曾报道发现了6个新的小鼠T-box基因Tbx1 - Tbx6,并描述了Tbx1 - Tbx5的表达模式(Bollag等,1994;Agulnik等,1996;Chapman等,1996;Gibson-Brown等,1996)。我们从原肠胚期小鼠cDNA文库中获得了编码全长Tbx6蛋白的cDNA克隆,并确定了Tbx6转录本在胚胎发生过程中的时空分布。该基因编码一个1.9 kb的转录本,其中一个开放阅读框编码一个540个氨基酸的蛋白,预计分子量为59 kDa。Tbx6定位于7号染色体,似乎与任何已知的突变都没有联系。不同于其他的小鼠T-box基因家族成员,Tbx6的表达是非常有限的,这些成员在来自所有胚层的各种组织中表达。Tbx6转录本首先在原肠胚期的原始条纹和新募集的近轴中胚层中被检测到。在发育后期,Tbx6的表达仅限于体前、近轴中胚层和尾芽,后者取代条纹成为中胚层的来源。在尾芽中的表达持续到交媾后12.5天。因此Tbx6的表达与Brachyury在原始条纹和尾芽中的表达重叠,尽管Brachyury在原始条纹中的表达较早。Brachyury也在第二域(节点和脊索)中表达,这与Tbx6不同。在交配后7.5天的纯合子突变胚中,Tbx6的表达不受影响。然而,一旦Brachyury表型在交配后8.5天变得明显,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。(C) 1996学术出版社,Inc.
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. (C) 1996 Academic Press, Inc.