Int J Biol Sci 2018; 14(6):667-681. doi:10.7150/ijbs.23815
VRTN is Required for the Development of Thoracic Vertebrae in Mammals
State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, 330045, China.
* These authors contributed equally to this work.
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
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