Meno C, Saijoh Y, Fujii H, Ikeda M, Yokoyama T, Yokoyama M, Toyoda Y, Hamada H
Tokyo Metropolitan Institute of Medical Science, Japan.
Nature. 1996 May 9;381(6578):151-5. doi: 10.1038/381151a0.
Examples of lateral asymmetry are often found in vertebrates, such as the heart being on the left side, but the molecular mechanism governing the establishment of this left-right (L-R) handedness is unknown. A diffusible morphogen may determine L-R polarity, but a likely molecule has not so far been identified. Here we report on the gene lefty, a member of the transforming growth factor-beta family, which may encode a morphogen for L-R determination. Lefty protein contains the cysteine-knot motif characteristic of this superfamily and is secreted as a processed form of relative molecular mass 25K-32K. Surprisingly, lefty is expressed in the left half of gastrulating mouse embryos. This asymmetric expression is very transient and occurs just before the first sign of lateral asymmetry appears. In the mouse mutants iv and inv, which cause situs inversus, the sites of lefty expression are inverted, indicating that lefty is downstream of iv and inv. These results suggest that lefty may be involved in setting up L-R asymmetry in the organ systems of mammals.
脊椎动物中常常能发现左右不对称的例子，比如心脏位于左侧，但控制这种左右旋性建立的分子机制尚不清楚。一种可扩散的形态发生素可能决定左右极性，但到目前为止尚未鉴定出可能的分子。在此我们报告基因lefty，它是转化生长因子-β家族的成员，可能编码一种用于确定左右的形态发生素。Lefty蛋白含有该超家族特有的半胱氨酸结基序，并以相对分子质量为25K - 32K的加工形式分泌。令人惊讶的是，lefty在原肠胚形成期的小鼠胚胎左侧一半表达。这种不对称表达非常短暂，且恰好在左右不对称的首个迹象出现之前发生。在导致内脏反位的小鼠突变体iv和inv中，lefty的表达位点发生了反转，这表明lefty位于iv和inv的下游。这些结果表明，lefty可能参与了哺乳动物器官系统中左右不对称的建立。
