Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning
Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning
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DOI：
10.1073/pnas.0912818107
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发表时间：
2010-03-23
影响因子：
11.1
通讯作者：
Harfe, Brian D.
中科院分区：
文献类型：
--
作者：
Bouldin, Cortney M.;Gritli-Linde, Amel;Harfe, Brian D.
Sonic Hedgehog（Shh）在发育肢芽的后间充质中的表达通过激活Hedgehog（Hh）信号通路调节发育肢的图案形成和生长。通过对Shh和Hh信号传导靶基因的分析，已经表明肢芽中胚层的激活是正常肢发育发生所必需的。相反，已经指出肢芽外胚层中的Hh信号传导不能发生，因为在该组织中尚未发现Hh信号传导途径的组分和Hh靶基因。然而，最近基于阵列的数据确定了激活Hh信号通路所必需的组分和肢芽外胚层中该通路的靶点。利用免疫组织化学和多种方法检测Hh信号传导的靶点，我们发现SHH蛋白和Hh信号传导的靶点存在于肢芽的外胚层，包括芽的顶端。为了直接测试外胚层Hh信号传导是否是正常肢体图案形成所需的，我们从顶端外胚层嵴（AER）中去除了Hh信号传导途径的重要组成部分Smo。AER中功能性Hh信号传导的丧失导致正常手指模式的破坏和额外轴后软骨凝聚的形成。这些数据表明，相反，以前的帐户，Hh信号通路是存在的，并要求在发展肢体AER正常的autopod发展。
Expression of Sonic Hedgehog (Shh) in the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developing limb by activation of the Hedgehog (Hh) signaling pathway. Through the analysis of Shh and Hh signaling target genes, it has been shown that activation in the limb bud mesoderm is required for normal limb development to occur. In contrast, it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the Hh signaling pathway and Hh target genes have not been found in this tissue. However, recent array-based data identified both the components necessary to activate the Hh signaling pathway and targets of this pathway in the limb bud ectoderm. Using immunohistochemistry and various methods of detection for targets of Hh signaling, we found that SHH protein and targets of Hh signaling are present in the limb bud ectoderm including the apex of the bud. To directly test whether ectodermal Hh signaling was required for normal limb patterning, we removed Smo, an essential component of the Hh signaling pathway, from the apical ectodermal ridge (AER). Loss of functional Hh signaling in the AER resulted in disruption of the normal digit pattern and formation of additional postaxial cartilaginous condensations. These data indicate that contrary to previous accounts, the Hh signaling pathway is present and required in the developing limb AER for normal autopod development.