The Reissner Fiber is Highly Dynamic in vivo and Controls Morphogenesis of the Spine

SummarySpine morphogenesis requires the integration of multiple musculoskeletal tissues with the nervous system. Cerebrospinal fluid (CSF) physiology is important for development and homeostasis of the central nervous system and its disruption has been linked to scoliosis in zebrafish [1, 2]. Suspended in the CSF is an enigmatic glycoprotein thread called the Reissner fiber, which is secreted from the subcomissural organ (SCO) in the brain and extends caudally through the central canal to where it terminates at the base of the spinal cord. In zebrafish,scospondinnull mutants are unable to assemble the Reissner fiber and fail to extend a straight body axis during embryonic development [3]. Here, we describe zebrafish hypomorphic missense alleles, which assemble the Reissner fiber and straighten the body axis during early embryonic development, yet progressively lose the fiber, concomitant with the emergence of body curvature, alterations in neuronal gene expression, and scoliosis in adults. Using an endogenously taggedscospondin-GFPzebrafish knock-in line, we directly visualized Reissner fiber dynamics during the normal development and during the progression of scoliosis, and demonstrate that the Reissner fiber is critical for the morphogenesis of the spine. Our study establishes a framework for future investigations of mechanistic roles of the Reissner fiber including its dynamic properties, molecular interactions, and how these processes are involved in the regulation of spine morphogenesis and scoliosis.HighlightsHypomorphic mutations in zebrafishscospondinresult in progressive scoliosisThe disassembly of the Reissner fiber inscospondinhypomorphic mutants results in the strong upregulation of neuronal receptors and synaptic transport componentsAn endogenous fluorescent knock-in allele ofscospondinreveals dynamic properties of the Reissner fiber during zebrafish developmentLoss of the Reissner fiber during larval development is a common feature of zebrafish scoliosis models