Research Paper Volume 12, Issue 18 pp 18603—18621

Muscle defects due to perturbed somite segmentation contribute to late adult scoliosis

Laura Lleras-Forero1,2, &, , Elis Newham3, , Stefan Teufel4, , Koichi Kawakami5, , Christine Hartmann4, , Chrissy L. Hammond3, , Robert D. Knight6, , Stefan Schulte-Merker1,2, ,

  • 1 Institute for Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU, Münster, Germany
  • 2 Hubrecht Institute-KNAW and University Medical Center Utrecht, CT, Utrecht, The Netherlands
  • 3 The School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK
  • 4 Institut für Muskuloskelettale Medizin (IMM), Abteilung Knochen- und Skelettforschung, Universitätsklinikum Münster, Germany
  • 5 Laboratory of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan
  • 6 Centre for Craniofacial and Regenerative Biology, King´s College London, London, UK

Received: March 3, 2020       Accepted: July 14, 2020       Published: September 25, 2020
How to Cite

Copyright: © 2020 Lleras-Forero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Scoliosis is an abnormal bending of the body axis. Truncated vertebrae or a debilitated ability to control the musculature in the back can cause this condition, but in most cases the causative reason for scoliosis is unknown (idiopathic). Using mutants for somite clock genes with mild defects in the vertebral column, we here show that early defects in somitogenesis are not overcome during development and have long lasting and profound consequences for muscle fiber organization, structure and whole muscle volume. These mutants present only mild alterations in the vertebral column, and muscle shortcomings are uncoupled from skeletal defects. None of the mutants presents an overt musculoskeletal phenotype at larval or early adult stages, presumably due to compensatory growth mechanisms. Scoliosis becomes only apparent during aging. We conclude that adult degenerative scoliosis is due to disturbed crosstalk between vertebrae and muscles during early development, resulting in subsequent adult muscle weakness and bending of the body axis.


dpf: days post fertilization; fss: Fused somite; tbx6: T-Box transcription factor 6; her1: human epidermal growth factor receptor 1; her7: hairy and enhancer of split related 7; hpf: hours post fertilization; CVM: congenital vertebral malformations.