LAUSR

Adolescent idiopathic scoliosis (IS), a disease characterized by 3D spinal curvatures, afflicts 3% of children worldwide. However, the underlying developmental basis for this disease has remained unknown. Recently, the teleost fish have emerged as robust models of IS. Using zebrafish, we have discovered that spinal curves are caused by loss of motile cilia function, which in turn results in defective CSF flow. Human IS can be caused by mutations in PTK7, and we find that cilia/CSF flow defects are also the basis of spinal curves in ptk7 zebrafish mutants. Thus, we propose that IS can be caused by disruptions to CSF flow during the growth phase, providing a novel mechanism for this prevalent disease. We also give evidence that spinal curves can be partially rescued by restoring cilia motility after curve onset, opening potential therapeutic avenues. Overall, our study provides new insight into spine formation and the maintenance of spine linearity.