An examination of the Chiropteran HoxD locus from an evolutionary perspective
An examination of the Chiropteran HoxD locus from an evolutionary perspective
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DOI：
10.1111/j.1525-142x.2008.00279.x
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发表时间：
2008-10
影响因子：
2.9
通讯作者：
Russell Ray;M. Capecchi
中科院分区：
文献类型：
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作者：
Russell Ray;M. Capecchi
Hox基因簇的复制被认为是一种机制，通过这种机制，新的Hox功能可以被开发，同时保留关键的祖先角色。然而，在四足动物中，特别是在哺乳动物中，已知受Hox基因影响的肢体结构形态存在很大的变异性，而没有进一步的Hox簇重复。缺乏进一步的重复表明，如果Hox基因在四足动物四肢的形态加工中发挥了直接作用，那么这些变化一定是来自Hox蛋白序列的变化，或者来自Hox基因表达的数量、时间和位置的变化。为了研究Hox基因的这种变化是否会在肢体发育中发挥作用，我们研究了蝙蝠中的HoxD基因座，这些蝙蝠具有高度发育的前肢和后肢。我们发现，而翼手目HoxD13蛋白是高度保守的，有一个扩展的HoxD13表达的翼手目前肢的后部，并进入前缘的翅膀膜。我们还能够发现已知HoxD肢体增强子全局控制区（GCR）的一些独特的谱系特异性序列变化。此外，小鼠转基因测定显示，翼手目GCR具有新的肢体增强子活性结构域，超出了人类GCR的报道。这些结果表明Hox基因表达的调节可能是以谱系特异性方式影响形态学变化同时保持祖先约束和簇完整性的机制。
SUMMARY Duplications of Hox gene clusters have been suggested as a mechanism whereby new Hox functions can be developed while preserving critical ancestral roles. However, in tetrapods, particularly in mammals, there is great variability in limb structure morphologies that are known to be affected by Hox genes without further Hox cluster duplications. The lack of further duplications suggests that if Hox genes have played a direct role in the morphological elaboration of tetrapod limbs, the changes must have come about from Hox protein sequence changes or from changes regarding the amount, time, and place of Hox gene expression. To investigate whether such changes to Hox genes could play a role in limb elaboration, we examined the HoxD locus in bats, which have both highly elaborated fore‐ and hindlimbs. We found that while the Chiropteran HoxD13 protein was highly conserved, there was an expansion of HoxD13 expression in the posterior portion of the Chiropteran forelimb and into the leading edge of the wing membrane. We were also able to uncover a number of unique lineage‐specific sequence changes to a known HoxD limb enhancer, the Global Control Region (GCR). Further, mouse transgenic assays showed that the Chiropteran GCR has new limb enhancer activity domains beyond that reported for the Human GCR. These results suggest that modulation of Hox gene expression may be a mechanism for effecting morphological change in lineage‐specific manner while maintaining ancestral constraints and cluster integrity.