VRTN is Required for the Development of Thoracic Vertebrae in Mammals

Abstract

Vertnin (<i>VRTN</i>) variants are associated with thoracic vertebral number (TVN) in pigs. However, the biological function of <i>VRTN</i> remains poorly understood. Here we first conducted a range of experiments to demonstrate that <i>VRTN</i> is a responsible gene for TVN and two causative variants in the regulatory region of <i>VRTN</i> 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 <i>VRTN</i> is essential for the development of thoracic vertebrae. <i>Vrtn</i>-null embryos display somitogenesis defect with the failure of axial rotation and fewer somites at the thoracic somite stage. Half of <i>Vrtn</i> 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 <i>VRTN</i> causative variants provide a robust tool to improve pork production by selecting the alleles increasing the number of thoracic vertebrae and ribs.