Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos
Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos
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DOI：
10.1046/j.1365-2443.1997.1400338.x
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发表时间：
1997-08-01
期刊：
影响因子：
2.1
通讯作者：
Hamada, H
中科院分区：
文献类型：
--
作者：
Meno, C;Ito, Y;Hamada, H
背景：脊椎动物在其器官的位置上有许多侧向不对称，但决定左右（L-R）不对称的分子基础在很大程度上仍然未知。TGF β相关基因lefty、nodal等在发育中的小鼠胚胎中呈L-R不对称表达，可能参与GR的测定。结果：在小鼠基因组中鉴定出两个高度保守的基因left -1和left -2。这两个基因在小鼠1号染色体上紧密相连。left -1和left -2在小鼠胚胎中均以L-R不对称方式表达。然而，这两个基因的主要表达域是不同的：left -1主要表达于腹侧神经管的左侧，而left -2则强烈表达于左侧的侧板中胚层。在iv和inv突变纯合的胚胎中，这两个基因的表达位点都会受到影响，要么是反向的，要么是双向的，这表明left -1和left -2是iv和inv的下游。尽管在培养细胞中，lefty-1和lefty嵌合蛋白不容易加工，但BMP2-Lefty嵌合蛋白可以加工成分泌形式。我们在爪蟾胚胎中检测了Lefty-1和Lefty-2的活性。在动物帽外植体中，Lefty-1和Lefty-2在没有中胚层诱导的情况下诱导神经细胞。因此，左撇子-1和左撇子-2的直接神经化活性似乎与BMP拮抗剂（如noggin和chordin）非常相似，这表明左撇子-1和左撇子-2的作用可能是局部拮抗位于小鼠胚胎左侧的组织中BMP（骨形态发生蛋白）介导的信号。结论：小鼠中存在两个左基因（left -1和left -2），它们均以LR不对称方式表达，位于iv和inv的下游。left -1和left -2在爪蟾胚胎中具有直接的神经化活性，类似于BMP拮抗剂的活性。
Background: Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left-right (L-R) asymmetries remains largely unknown. TGF beta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in GR determination.Results: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)mediated signals in tissues positioned on the left side of the mouse embryos.Conclusion: There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a LR asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.