Infante Carlos R, Mihala Alexandra G, Park Sungdae, Wang Jialiang S, Johnson Kenji K, Lauderdale James D, Menke Douglas B
Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Dev Cell. 2015 Oct 12;35(1):107-19. doi: 10.1016/j.devcel.2015.09.003. Epub 2015 Oct 1.
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 that 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.
羊膜动物的阴茎和四肢在形态上有显著差异，但在早期发育中具有共同的信号传导和基因表达模式。到目前为止，生殖器官和四肢的转录网络在多大程度上也共享顺式调控元件仍未得到探索。我们发现许多四肢增强子保留在蛇的基因组中，这表明这些元件可能在非四肢组织中发挥作用。与此一致的是，我们对小鼠和绿安乐蜥顺式调控活性的分析表明，胚胎四肢和生殖器官中的增强子活性模式有很大重叠。在小鼠中，Tbx4的增强子HLEB缺失会导致后肢和生殖器官出现缺陷，确立了这种四肢-生殖增强子对这些不同附属器官发育的重要性。进一步分析表明，蛇的HLEB失去了后肢增强子功能，但保留了生殖活性。我们的研究结果确定了Tbx4在生殖发育中的作用，并突出了四肢和生殖器官在顺式调控活性方面的深刻相似性。
