IS is a highly prevalent spinal deformity that afflicts upwards of 4% of the population, yet the underlying causes of this disease are unknown.Population-based association studies and next-generation sequencing approaches have identified numerous disease-associated genetic loci; however, a lack of appropriate animal models has hindered understanding of the biological origins of disease.Fish demonstrate a natural susceptibility towards developing spinal curvatures and several zebrafish mutants have recently been demonstrated to faithfully model defining attributes of human IS.Analysis of these zebrafish IS models demonstrates a novel role for motile cilia-directed cerebrospinal fluid (CSF) flow in normal spine morphogenesis, and implicate cilia motility and CSF flow defects as the underlying biological cause of spinal curvatures.