VRTN is Required for the Development of Thoracic Vertebrae in Mammals.
VRTN is Required for the Development of Thoracic Vertebrae in Mammals.
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VRTN 是哺乳动物胸椎发育所必需的
DOI：
10.7150/ijbs.23815
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发表时间：
2018
影响因子：
9.2
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Duan Y;Zhang H;Zhang Z;Gao J;Yang J;Wu Z;Fan Y;Xing Y;Li L;Xiao S;Hou Y;Ren J;Huang L
Vertnin（VRTN）变体与猪的胸椎数量（TVN）相关。然而，VRTN的生物学功能仍然知之甚少。在这里，我们首先进行了一系列的实验，以证明VRTN是一个负责的基因TVN和VRTN的调节区的两个致病变体相加调节TVN。然后，我们表明，VRTN是一种新的DNA结合转录因子，因为它只定位在细胞核中，结合到DNA在全基因组范围内，并调节一组含有VRTN结合基序的基因的转录。接下来，我们说明VRTN是必不可少的胸椎的发展。vrtn基因敲除的胚胎在胸体节阶段表现为体节发生缺陷，轴向旋转失败，体节数量减少。一半的Vrtn杂合子小鼠表现出脊柱发育异常，胸椎和肋骨比野生型小鼠少。最后，我们揭示了VRTN可以通过Notch信号通路调节体节的分割。这些发现推进了我们对哺乳动物胸椎发育机制的理解，VRTN致病变体提供了一个强大的工具，通过选择增加胸椎和肋骨数量的等位基因来提高猪肉产量。
Vertnin (VRTN) variants are associated with thoracic vertebral number (TVN) in pigs. However, the biological function of VRTN remains poorly understood. Here we first conducted a range of experiments to demonstrate that VRTN is a responsible gene for TVN and two causative variants in the regulatory region of VRTN additively regulate TVN. Then, we show that VRTN is a novel DNA-binding transcription factor as it localizes exclusively in the nucleus, binds to DNA on a genome-wide scale and regulates the transcription of a set of genes that harbor VRTN binding motifs. Next, we illustrate that VRTN is essential for the development of thoracic vertebrae. Vrtn-null embryos display somitogenesis defect with the failure of axial rotation and fewer somites at the thoracic somite stage. Half of Vrtn heterozygous mice show abnormal spinal development with fewer thoracic vertebrae and ribs than their wild-type littermates. Lastly, we reveal that VRTN could modulate somite segmentation via the Notch signaling pathway. The findings advance our understanding of the mechanisms underlying the development of thoracic vertebrate in mammals, and VRTN causative variants provide a robust tool to improve pork production by selecting the alleles increasing the number of thoracic vertebrae and ribs.
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影响因子：
64.8
作者：
Jiang, YJ;Aerne, BL;Lewis, J
通讯作者：
Lewis, J
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS
影响因子：
2.6
作者：
Borchers, N;Reinsch, N;Kalm, E
通讯作者：
Kalm, E
DOI：
10.1073/pnas.1401392111
发表时间：
2014-08-05
影响因子：
11.1
作者：
Galis, Frietson;Carrier, David R.;ten Broek, Clara M. A.
通讯作者：
ten Broek, Clara M. A.
影响因子：
2.8
作者：
Dao, Debbie Y.;Yang, Xue;Flick, Lisa M.;Chen, Di;Hilton, Matthew J.;O'Keefe, Regis J.
通讯作者：
O'Keefe, Regis J.