Reissner fibre-induced urotensin signalling from cerebrospinal fluid-contacting neurons prevents scoliosis of the vertebrate spine

Reissner fibre (RF), discovered by the 19th-century German anatomist Ernst Reissner, is a filamentous structure present in cerebrospinal fluid (CSF). RF forms by aggregation of a glycoprotein called SCO-spondin (Sspo), but its function has remained enigmatic. Recent studies have shown that zebrafish sspo mutants develop a curved embryonic body axis. Zebrafish embryos with impaired cilia motility also develop curved bodies, which arises from failure of expression of urotensin related peptide ( urp ) genes in CSF-contacting neurons (CSF-cNs), impairing downstream signalling in trunk muscles. Here, we show that sspo mutants can survive into adulthood, but display severe curvatures of the vertebral column, resembling the common human spine disorder idiopathic scoliosis (IS). sspo mutants also exhibit significant reduction of urp gene expression from CSF-cNs. Consistent with epinephrine in CSF being bound by RF and required for urp expression, treating sspo mutants with this catecholamine rescued expression of the urp genes and axial defects. More strikingly, providing Urp2, specifically in the CSF-cNs, rescued body curvature of sspo homozygotes during larval stages as well as in the adult. These findings bridge existing gaps in our knowledge between cilia motility, RF, Urp signalling and spine deformities, and suggest that targeting the Urotensin pathway could provide novel therapeutic avenues for IS.