Functional differences among Xenopus nodal-related genes in left-right axis determination.
Functional differences among Xenopus nodal-related genes in left-right axis determination.
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DOI：
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发表时间：
1997-09
期刊：
影响因子：
4.6
通讯作者：
K. Sampath;A. M. Cheng;A. Frisch;C. Wright
中科院分区：
文献类型：
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作者：
K. Sampath;A. M. Cheng;A. Frisch;C. Wright
以前已经注意到鸡，小鼠和青蛙胚胎之间的不对称的胚胎相关基因表达和胚胎部位，这意味着进化保守的作用，左右规格。在原肠胚形成过程中表达的四个非洲爪蟾胚胎相关基因中，只有Xnr-1在神经胚/尾芽阶段的左侧板中胚层中单侧重新表达。在这里，我们表明，Xnr-1的不对称表达，可以通过右侧显微注射的RNA编码活性爪蟾刺猬蛋白的双侧对称。此外，我们提供的第一个证据表明，Xnr-1表达本身是一个因果因素，在左右轴的决定。当表达Xnr-1的质粒单侧传递到非洲爪蟾胚胎的右侧时，在40%的存活胚胎中诱导了心脏和肠道的反向偏侧性（同源性逆转），而另外10-20%的胚胎显示心脏或肠道单独逆转（异位）。这种对偏侧性的影响是Xnr-1所特有的，因为Xnr-2和Xnr-3质粒都没有这种活性。此外，我们发现，Xnr-1和Xnr-2，这两个已被定义为中胚层诱导剂过表达研究，显示其诱导背中胚层的能力的定量差异。总之，这些研究结果表明，各种Xnrs执行实质上不同的功能在非洲爪蟾胚胎发生。此外，他们强烈支持的假设，即左侧板的表达的脊椎动物胚胎的不对称性的决定是一个致病因素。
An association has been noted previously in chick, mouse and frog embryos between asymmetric nodal-related gene expression and embryonic situs, implying an evolutionarily conserved role in left-right specification. Of the four Xenopus nodal-related genes expressed during gastrulation, only Xnr-1 is re-expressed unilaterally in the left lateral plate mesoderm at neurula/tailbud stages. Here, we show that the asymmetric expression of Xnr-1 can be made bilaterally symmetric by right-sided microinjection of RNA encoding active Xenopus hedgehog proteins. Moreover, we provide the first evidence that Xnr-1 expression per se is a causal factor in left-right axis determination. When plasmids expressing Xnr-1 were delivered unilaterally to the right side of Xenopus embryos, a reversed laterality of both the heart and gut (homotaxic reversal) was induced in 40% of surviving embryos, while an additional 10-20% showed reversal of the heart or gut alone (heterotaxia). This effect on laterality was specific to Xnr-1, since neither Xnr-2 nor Xnr-3 plasmids had this activity. In addition, we find that Xnr-1 and Xnr-2, which have both been defined as mesoderm inducers from overexpression studies, show quantitative differences in their ability to induce dorsal mesoderm. Together, these findings suggest that the various Xnrs perform substantially different functions during Xenopus embryogenesis. Moreover, they strongly support the hypothesis that left lateral plate expression of nodal-related genes is a causative factor in the determination of asymmetry in vertebrate embryos.