Critical role for Tbx6 in mesoderm specification in the mouse embryo
Critical role for Tbx6 in mesoderm specification in the mouse embryo
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DOI：
10.1016/s0925-4773(03)00066-2
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发表时间：
2003-07-01
影响因子：
2.6
通讯作者：
Papaioannou, VE
中科院分区：
文献类型：
--
作者：
Chapman, DL;Cooper-Morgan, A;Papaioannou, VE
Tbx6 是转录因子基因 T-box 家族的成员。该基因的两个突变等位基因证实 Tbx6 参与整个胚胎长度体节的规范和模式化。无效等位基因 Tbx6(tm/Pa) 会导致颈体节的异常模式和更多后轴旁中胚层的不正确规格，从而形成异位神经管。在本研究中，我们利用该等位基因进一步研究Tbx6基因的作用机制并研究可能的遗传相互作用。我们测试了 Tbx6(tm/Pa) /Tbx6(tm/Pa) 细胞在异位、体外和体内嵌合体中的发育和分化潜力。我们还记录了突变尾芽中的细胞增殖和细胞死亡，试图解释 Tbx6 突变胚胎中尾芽增大的机制。我们的结果表明，一旦缺乏Tbx6的后细胞穿过原条，它们的分化就会受到特定的发育限制，但前体节或Tbx6无效胚胎干（ES）细胞的分化没有限制。我们进一步证明 Tbx6 null ES 细胞无法在嵌合胚胎中填充后体节。为了发现不同的 T-box 蛋白是否在表达重叠区域的相同下游靶标上相互作用，我们探索了 Tbx6 和 T (Brachyury) 在遗传杂交中的潜在相互作用。我们的结果表明，T-Wis 突变是 Tbx6(tm/Pa) 突变的上位性，并且没有明显的遗传相互作用。然而，Tbx6(tm/Pa) 的纯合性和 T-Wis 突变的杂合性在表型水平上显示出组合相互作用。 (C) 2003 Elsevier Ireland Ltd. 保留所有权利。
Tbx6 is a member of the T-box family of transcription factor genes. Two mutant alleles of this gene establish that Tbx6 is involved in both the specification and patterning of the somites along the entire length of the embryo. The null allele, Tbx6(tm/Pa), causes abnormal patterning of the cervical somites and improper specification of more posterior paraxial mesoderm, such that it forms ectopic neural tubes. In this study, we use this allele to further investigate the mechanism of action of the Tbx6 gene and investigate possible genetic interactions. We have tested the developmental and differentiation potential of Tbx6(tm/Pa) /Tbx6(tm/Pa) cells in ectopic sites, in vitro, and in chimeras in vivo. We have also documented cell proliferation and cell death in mutant tail buds in an attempt to explain the mechanism of tail bud enlargement in the Tbx6 mutant embryos. Our results indicate specific developmental restrictions on the differentiation of posterior cells lacking Tbx6, once they have traversed the primitive streak, but no restrictions in differentiation of anterior somites, or of Tbx6 null embryonic stem (ES) cells. We further demonstrate that Tbx6 null ES cells fail to populate posterior somites in chimeric embryos. 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. Our results reveal that the T-Wis mutation is epistatic to the Tbx6(tm/Pa) mutation and that there is no apparent genetic interaction. However, homozygosity for Tbx6(tm/Pa) and heterozygosity for T-Wis mutation shows a combinatorial interaction at the phenotypic level. (C) 2003 Elsevier Ireland Ltd. All rights reserved.