Meno C, Ito Y, Saijoh Y, Matsuda Y, Tashiro K, Kuhara S, Hamada H
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Genes Cells. 1997 Aug;2(8):513-24. doi: 10.1046/j.1365-2443.1997.1400338.x.
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. TGFbeta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination.
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.
There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a L-R 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.
脊椎动物器官位置存在众多左右不对称性，但左右不对称性确定的分子基础仍大多未知。诸如Lefty和Nodal等与转化生长因子β（TGFβ）相关的基因在发育中的小鼠胚胎中呈左右不对称表达，可能参与左右不对称性的确定。
我们在小鼠基因组中鉴定出两个高度保守的基因，Lefty - 1和Lefty - 2。这两个基因在小鼠1号染色体上紧密连锁。Lefty - 1和Lefty - 2在小鼠胚胎中均以左右不对称的方式表达。然而，这两个基因的主要表达结构域不同：Lefty - 1的表达主要局限于腹侧神经管左侧，而Lefty - 2在左侧侧板中胚层中强烈表达。在导致内脏反位的iv和inv突变纯合子胚胎中，两个基因的表达位点均受影响，要么反转要么双侧改变，表明Lefty - 1和Lefty - 2位于iv和inv的下游。尽管Lefty - 1和Lefty - 2前体蛋白在培养细胞中不易加工，但BMP2 - Lefty嵌合蛋白可加工成分泌形式。我们在非洲爪蟾胚胎中检测了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，Lefty - 1和Lefty - 2的直接神经诱导活性似乎与诸如Noggin和Chordin等BMP拮抗剂的活性非常相似，这表明Lefty - 1和Lefty - 2的作用可能是在小鼠胚胎左侧组织中局部拮抗BMP（骨形态发生蛋白）介导的信号。
小鼠中有两个Lefty基因（Lefty - 1和Lefty - 2），它们均以左右不对称的方式表达，且位于iv和inv的下游。Lefty - 1和Lefty - 2在非洲爪蟾胚胎中具有直接神经诱导活性，类似于BMP拮抗剂的活性。
