Multiple left-right asymmetry defects in Shh-/- mutant mice unveil a convergence of the Shh and retinoic acid pathways in the control of Lefty-1
Multiple left-right asymmetry defects in Shh-/- mutant mice unveil a convergence of the Shh and retinoic acid pathways in the control of Lefty-1
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DOI：
10.1073/pnas.96.20.11376
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Belmonte, JCI
中科院分区：
文献类型：
--
作者：
Tsukui, T;Capdevila, J;Belmonte, JCI
Sonic hedgehog（Shh）基因在鸡胚Hensen氏结中的不对称表达在左右不对称的遗传级联反应中起着关键作用，但其在其他脊椎动物中的左右特异性表达尚不清楚。我们发现，缺乏Shh的小鼠胚胎显示出多种偏侧性缺陷，包括肺左异构，心脏循环的改变，以及轴向旋转的随机化。Shh（-/-）胚胎中不存在左特异性基因Lefty-1的表达，这表明观察到的偏侧性缺陷可能是缺乏Lefty-1的结果。我们还表明，视黄酸（RA）控制左-1的表达在下游或平行于Shh的途径。此外，我们提供的证据表明，RA控制整个脊椎动物物种的左右发展。因此，Shh和RA在左右特化中的作用确实在脊椎动物中是保守的，并且Shh和RA通路在Lefty-1的控制中会聚。
Asymmetric expression of Sonic hedgehog (Shh) in Hensen's node of the chicken embryo plays a key role in the genetic cascade that controls left-right asymmetry, but its involvement in left-right specification in other vertebrates remains unclear. We show that mouse embryos lacking Shh display a variety of laterality defects, including pulmonary left isomerism, alterations of heart looping, and randomization of axial turning. Expression of the left-specific gene Lefty-1 is absent in Shh(-/-) embryos, suggesting that the observed laterality defects could be the result of the lack of Lefty-1. We also demonstrate that retinoic acid (RA) controls Lefty-1 expression in a pathway downstream or parallel to Shh. Further, we provide evidence that RA controls left-right development across vertebrate species. Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1.