Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus
Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus
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DOI：
10.1038/381158a0
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发表时间：
1996-05-09
期刊：
影响因子：
64.8
通讯作者：
Kuehn, MR
中科院分区：
文献类型：
--
作者：
Lowe, LA;Supp, DM;Kuehn, MR
脊椎动物具有典型的、保守的左-右（L-R）内脏不对称，例如左心。在人类中，L-R发育的改变可能具有严重的临床意义，包括心脏缺陷(1)。尽管人们对胚胎L-R轴是如何建立的知之甚少，但最近在鸡胚胎中的一项研究揭示了几个先前克隆的基因的L-R不对称表达，包括Cnr-1（鸡淋巴结相关-1），并表明这种L-R分子不对称可能对随后的内脏形态发生很重要(2)。在这里，我们发现nodal(3)在类似阶段的小鼠中不对称表达，Xnr-1 (Xenopus nodal相关-1)(4)在青蛙中也不对称表达。我们还研究了两种干扰L-R发育的小鼠突变中的淋巴结表达，即内脏逆位（iv）(5)，其中L-R不对称的分配显然是随机的，个体正常发育或镜像反向发育（position inversus），以及胚胎翻转反转（inv）(6)，其中所有个体都发育为逆位。在这两种情况下，节点表达都受到了显著的影响，被逆转或转化为对称。这些结果进一步支持了节点和节点相关基因在解释和传递脊椎动物L-R模式信息中的关键作用。据我们所知，我们的结果提供了第一个直接证据，证明在形态L-R不对称出现之前，iv和inv正常功能良好。
VERTEBRATES have characteristic and conserved left-right (L-R) visceral asymmetries, for example the left-sided heart. In humans, alterations of L-R development can have serious clinical implications, including cardiac defects(1). Although little is known about how the embryonic L-R axis is established, a recent study in the chick embryo revealed L-R asymmetric expression of several previously cloned genes, including Cnr-1 (for chicken nodal-related-1), and indicated how this L-R molecular asymmetry might be important for subsequent visceral morphogenesis(2). Here we show that nodal(3) is asymmetrically expressed in mice at similar stages, as is Xnr-1 (for Xenopus nodal related-1)(4) in frogs. We also examine nodal expression in two mouse mutations that perturb L-R development, namely situs inversus viscerum (iv)(5), in which assignment of L-R asymmetry is apparently random and individuals develop either normally or are mirror-image-reverse (situs inversus), and inversion of embryonic turning (inv)(6), in which all individuals develop with situs inversus. In both, nodal expression is strikingly affected, being reversed or converted to symmetry. These results further support a key role for nodal and nodal-related genes in interpreting and relaying L-R patterning information in vertebrates. To our knowledge, our results provide the first direct evidence that iv and inv normally function well before the appearance of morphological L-R asymmetry.