MRC Human Genetics Unit at the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Trends Genet. 2012 Aug;28(8):364-73. doi: 10.1016/j.tig.2012.03.012. Epub 2012 Apr 24.
Human hands and feet contain bones of a particular size and shape arranged in a precise pattern. The secreted factor sonic hedgehog (SHH) acts through the conserved hedgehog (Hh) signaling pathway to regulate the digital pattern in the limbs of tetrapods (i.e. land-based vertebrates). Genetic analysis is now uncovering a remarkable set of pathogenetic mutations that alter the Hh pathway, thus compromising both digit number and identity. Several of these are regulatory mutations that have the surprising attribute of misdirecting expression of Hh ligands to ectopic sites in the developing limb buds. In addition, other mutations affect a fundamental structural property of the embryonic cell that is essential to Hh signaling. In this review, we focus on the role that the Hh pathway plays in limb development, and how the many human genetic defects in this pathway are providing clues to the mechanisms that regulate limb development.
人类的手和脚包含特定大小和形状的骨头，这些骨头以精确的模式排列。分泌的因子 sonic hedgehog (SHH) 通过保守的 hedgehog (Hh) 信号通路发挥作用，调节四足动物（即陆地脊椎动物）肢体的数字模式。遗传分析现在揭示了一组显著的致病突变，这些突变改变了 Hh 通路，从而损害了数字的数量和身份。其中一些是调节突变，它们具有令人惊讶的属性，即将 Hh 配体的表达错误引导到发育中的肢芽的异位部位。此外，其他突变影响胚胎细胞的基本结构特性，这对 Hh 信号至关重要。在这篇综述中，我们重点介绍了 Hh 通路在肢体发育中的作用，以及该通路中的许多人类遗传缺陷如何为调节肢体发育的机制提供线索。
