PUBLICATION
Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis
- Authors
- Van Gennip, J.L.M., Boswell, C.W., Ciruna, B.
- ID
- ZDB-PUB-181215-18
- Date
- 2018
- Source
- Science advances 4: eaav1781 (Journal)
- Registered Authors
- Ciruna, Brian
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/pharmacology
- Biomarkers
- Disease Models, Animal
- Disease Progression
- Immunologic Factors/immunology
- Immunomodulation
- Morphogenesis
- Phenotype*
- Receptor Protein-Tyrosine Kinases/metabolism
- Scoliosis/etiology*
- Scoliosis/metabolism*
- Scoliosis/pathology
- Scoliosis/therapy
- Signal Transduction*
- Spine/metabolism*
- Spine/pathology
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 30547092 Full text @ Sci Adv
Citation
Van Gennip, J.L.M., Boswell, C.W., Ciruna, B. (2018) Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis. Science advances. 4:eaav1781.
Abstract
The etiopathogenesis of idiopathic scoliosis (IS), a highly prevalent spinal deformity that occurs in the absence of obvious congenital or physiological abnormalities, is poorly understood. Although recent zebrafish genetic studies have linked cilia motility and cerebrospinal fluid (CSF) flow defects with scoliosis progression, underlying mechanisms were not identified. Here, we use next-generation sequencing and conditional genetic methodologies to define the spatial and biological origins of spinal curve formation in ptk7 mutant zebrafish, a faithful IS model. We demonstrate that focal activation of proinflammatory signals within the spinal cord is associated with, and sufficient for, induction of spinal curvatures. Furthermore, administration of acetylsalicylic acid (aspirin) or N-acetylcysteine (NAC) to juvenile ptk7 mutants significantly reduces the incidence and/or severity of scoliosis phenotypes. Together, our results implicate neuroinflammation, downstream of CSF defects, in spinal curve formation and provide intriguing evidence that simple immunomodulating therapies might prove effective in managing idiopathic-like spinal deformities.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping