SCO-Spondin Defects and Neuroinflammation Identified as Conserved Mechanisms Driving Severe Spine Deformity Across Genetic Models of Idiopathic Scoliosis

Development: How the Reissner Fiber Keeps Our Back Straight

“…Ultimately, those abnormalities progress into severe 3D curvatures of the spine in adult zebrafish. Similarly to the previously reported scospondin mutant [11], Rose et al show that their mutant has no obvious cilia defects [5]. In line with another report showing the cilia mutant rpgrip1l with both spine curvatures and a loss of Reissner fiber at juvenile stages [15], these results place the Reissner fiber between cilia function and body axis formation both at embryonic and juvenile stages (Figure 1).…”

“…To understand the aetiology of idiopathic scoliosis, Rose et al and Troutwine et al took advantage of a forward genetic screen to identify mutants that display spine curvatures at juvenile or adult stages [5,6]. Upon whole-genome sequencing of identified mutants, both studies revealed mutations in the scospondin gene affecting the formation of the Reissner fiber.…”

“…This trait has been exploited to establish zebrafish working models of idiopathic scoliosis that appear to faithfully recapitulate the human disease [3,4]. In this issue of Current Biology, Rose et al and Troutwine et al elegantly provide a functional link between scoliosis in zebrafish and a curious protein structure threading through the central canal, called the Reissner fiber [5,6].…”

Spinal sensory neurons project onto the hindbrain to stabilize posture and enhance locomotor speed

“…[31][32][33][34][35][36][37] Cerebrospinal fluid-contacting neurons (CSF-cNs) form together with the Reissner fiber, 31,32,38 a sensory system that detects spinal curvature 34,35,39,40 and, in turn, shapes spine morphogenesis. 34,[41][42][43][44] CSF-cN mechanosensory function relies on the transient receptor potential channel polycystic kidney disease 2-like 1 (PKD2L1). 34,37 In the spinal cord, the pkd2l1 promoter specifically drives expression in CSF-cNs.…”

Spinal sensory neurons project onto hindbrain to stabilize posture and enhance locomotor speed

“…In addition to classical polysynaptic proprioceptive sensory pathways originating from the peripheral nervous system, investigations over the last decade have revealed a novel and highly conserved mechanosensory system in the spinal cord 31–37 . Cerebrospinal fluid-contacting neurons (CSF-cNs) form together with the Reissner fiber 31, 32, 38 a sensory system that detects spinal curvature 34, 35, 39, 40 and in turn, shapes spine morphogenesis 34, 41–44 . CSF-cN mechanosensory function relies on the transient receptor potential channel PKD2L1 34, 37 .…”