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Int J Biol Sci 2018; 14(6):667-681. doi:10.7150/ijbs.23815

Research Paper

VRTN is Required for the Development of Thoracic Vertebrae in Mammals

Yanyu Duan*, Hui Zhang*, Zhen Zhang, Jun Gao, Jie Yang, Zhongping Wu, Yin Fan, Yuyun Xing, Lin Li, Shijun Xiao, Yong Hou, Jun Ren, Lusheng Huang

State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, 330045, China.
* These authors contributed equally to this work.

Abstract

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.

Keywords: VRTN, transcription factor, thoracic vertebrae, somitogenesis

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
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. VRTN is Required for the Development of Thoracic Vertebrae in Mammals. Int J Biol Sci 2018; 14(6):667-681. doi:10.7150/ijbs.23815. Available from http://www.ijbs.com/v14p0667.htm