Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia
Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia
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DOI：
10.1242/dev.01885
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发表时间：
2005-07-01
期刊：
影响因子：
4.6
通讯作者：
Duboule, D
中科院分区：
文献类型：
--
作者：
Cobb, J;Duboule, D
哺乳动物的HOX基因编码转录因子，这些转录因子对于沿着不同的体轴正常的形态发生至关重要。尽管它们具有广泛的结构和功能特征，但它们的目标基因的性质仍然难以捉摸。我们已经解决了这个问题，使用DNA微阵列来筛选其在发育中的远端前肢和生殖器隆起中的表达在缺乏完整的Hoxd基因补体的情况下显着改变的基因。这种比较方法不仅确定了特定的候选基因，而且还允许检查不同组织中相似的HOX表达模式是否导致相同或不同下游基因的调控。我们在这里报告了一组潜在的靶基因，其中大多数以前并不知道在肢体或生殖器芽发育的早期阶段发挥作用。有趣的是，我们发现这些候选基因中的大多数在这两种结构中都有不同的表达，尽管通常是在不同的时间。这支持了这样的观点，即这两个附录都涉及类似的基因控制，包括HOX基因家族的上游和下游。这些结果突显了这些相当不同的身体部分之间令人惊讶的机械关系，并提出了一种共同的发育策略，以建立身体最远端的附件结构，即手指和阴茎/阴蒂。
Mammalian Hox genes encode transcription factors that are crucial for proper morphogenesis along the various body axes. Despite their extensive structural and functional characterization, the nature of their target genes remains elusive. We have addressed this question by using DNA microarrays to screen for genes whose expression in developing distal forelimbs and genital eminences was significantly modified in the absence of the full Hoxd gene complement. This comparative approach not only identified specific candidate genes, but also allowed the examination of whether a similar Hox expression pattern in distinct tissues leads to the modulation of the same or different downstream genes. We report here a set of potential target genes, most of which were not previously known to play a role in the early stages of either limb or genital bud development. Interestingly, we find that the majority of these candidate genes are differentially expressed in both structures, although often at different times. This supports the idea that both appendices involve similar genetic controls, both upstream and downstream of the Hox gene family. These results highlight the surprising mechanistic relationship between these rather different body parts and suggest a common developmental strategy to build up the most distal appendicular structures of the body, i.e. the digits and the penis/clitoris.