Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.
Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.
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DOI：
10.1016/j.devcel.2015.09.003
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发表时间：
2015-10-12
影响因子：
11.8
通讯作者：
Menke DB
中科院分区：
文献类型：
--
作者：
Infante CR;Mihala AG;Park S;Wang JS;Johnson KK;Lauderdale JD;Menke DB
阴茎和四肢在形态上有很大的不同，但在早期发育中有相同的信号和基因表达模式。到目前为止，在何种程度上生殖器和肢体转录网络也共享顺式调控元件仍有待探讨。我们发现许多肢体增强子保留在蛇的基因组中，这表明这些元素可能在非肢体组织中发挥作用。与此一致，我们对小鼠和Anolis蜥蜴顺式调节活性的分析表明，胚胎四肢和生殖器中的增强子活性模式重叠严重。在小鼠中，Tbx 4的增强子HLEB的缺失会导致后肢和生殖器的缺陷，从而确立了这种肢体-生殖器增强子对这些不同附件发育的重要性。进一步的分析表明，蛇的HLEB失去了后肢增强子功能，但保留了生殖器活动。我们的研究结果确定了Tbx 4在生殖器发育中的作用，并强调了四肢和生殖器之间顺式调节活性的深刻相似性。
The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia.