A dual role for Hox genes in limb anterior-posterior asymmetry
A dual role for Hox genes in limb anterior-posterior asymmetry
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DOI：
10.1126/science.1096049
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发表时间：
2004-06-11
期刊：
影响因子：
56.9
通讯作者：
Duboule, D
中科院分区：
文献类型：
--
作者：
Zákány, J;Kmita, M;Duboule, D
前肢到后肢的模式，即我们的手指形状不同的过程，是肢体发育的一个关键方面。它取决于Sonic hedgehog基因（Shh）在后肢芽中的局部表达及其扩散产物的形态发生潜能。通过对小鼠HoxD簇的倒置和大量缺失，我们发现在肢体芽中Hoxd11、Hoxd12和Hoxd13的早期共线表达的扰动导致不对称性的丧失。异位的Hox基因表达引发Shh转录异常，进而诱导趾中Hox基因的对称表达，从而产生双后肢。我们得出结论，Hox基因产物的早期后向限制建立了一个前后预模式，这决定了Shh的局部激活。该信号随后通过促进Hoxd基因的晚期表达而转化为手指形态的不对称，这两个共线过程依赖于相反的基因组地形，上游和下游Shh信号。
Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of Sonic hedgehog (Shh) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse HoxD cluster, we found that a perturbation in the early collinear expression of Hoxd11, Hoxd12, and Hoxd13 in limb buds led to a loss of asymmetry. Ectopic Hox gene expression triggered abnormal Shh transcription, which in turn induced symmetrical expression of Hox genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of Hox gene products sets up an anterior-posterior prepattern, which determines the localized activation of Shh. This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of Hoxd genes, two collinear processes relying on opposite genomic topographies, upstream and downstream Shh signaling.