Abstract
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.
Highlights
As the human population gets older, the effects of aging of the musculoskeletal system and its consequences on the quality of life have become increasingly important to understand
These include several genes involved in the somite clock such as the Notch receptor DLL3 [27, 28], the T-box gene TBX6 [29], MESP2 [30], HES7 [31, 32], LFNG [33] and RIPPLY2 [34]
In order to understand more about the link between the somite clock and adult degenerative scoliosis, we analysed zebrafish mutants defective for three clock segmentation genes: her1-/-; her7 -/, tbx6-/- and her1-/-; her7-/-; tbx6-/
Summary
As the human population gets older, the effects of aging of the musculoskeletal system and its consequences on the quality of life have become increasingly important to understand. Diseases that result in bending of the spine are more common in elderly populations. Camptocormia (a 45 degree anterior bent of the lower joints of the spine) has an average age of onset of 66 years [1] and from the age of 50 years the prevalence of thoracic scoliosis is 24.2% [2]. Cobb angle ≥ 10°, and can be divided into two classes: 1) idiopathic, where the patient has a history of adolescent idiopathic scoliosis, which progresses and worsens with age; 2) de novo, without previous symptoms or presence of scoliosis before onset of adult symptoms [4]. De novo scoliosis is becoming one of the most common clinical presentations found in the aging spine [5]. Mutations in genes associated with the Notch-Delta pathway and the segmentation clock genes have been found in some congenital scoliosis patients [6]
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