文章基本信息

标题：Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model
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作者：Anne Meyer-Miner ; Jenica L.M. Van Gennip ; Katrin Henke 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-20
DOI：10.1016/j.isci.2022.105028
语种：English
出版社：Elsevier
摘要：SummaryIdiopathic scoliosis (IS) refers to abnormal spinal curvatures that occur in the absence of vertebral or neuromuscular defects. IS accounts for 80% of human spinal deformity, afflicts ∼3% of children worldwide, yet pathogenic mechanisms are poorly understood. A key role for cerebrospinal fluid (CSF) homeostasis in zebrafish spine development has been identified. Specifically, defects in cilia motility of brain ependymal cells (EC), CSF flow, and/or Reissner fiber (RF) assembly are observed to induce neuroinflammation, oxidative stress, abnormal CSF-contacting neuron activity, and urotensin peptide expression, all associating with scoliosis. However, the functional relevance of these observations to IS remains unclear. Here we characterize zebrafishkatnb1mutants as a new IS model. We define essential roles for Katnb1 in motile ciliated lineages, uncouple EC cilia and RF formation defects from spinal curvature, and identify abnormal CSF flow and cell stress responses as shared pathogenic signatures associated with scoliosis across diverse zebrafish models.Graphical abstractDisplay OmittedHighlights•Characterizekatnb1mutant zebrafish as a new model of idiopathic scoliosis (IS)•Define critical role for Katnb1 in motile ciliated lineages, including choroid plexus•Uncouple ependymal cell cilia and Reissner fiber formation defects from spinal curves•Identify abnormal CSF flow and cell stress response as common signatures linked to ISMolecular genetics; Molecular biology experimental approach; Model organism.