Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model
Summary: Idiopathic 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 fl...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222013001 |
| _version_ | 1798036669825286144 |
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| author | Anne Meyer-Miner Jenica L.M. Van Gennip Katrin Henke Matthew P. Harris Brian Ciruna |
| author_facet | Anne Meyer-Miner Jenica L.M. Van Gennip Katrin Henke Matthew P. Harris Brian Ciruna |
| author_sort | Anne Meyer-Miner |
| collection | DOAJ |
| description | Summary: Idiopathic 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 zebrafish katnb1 mutants 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. |
| first_indexed | 2024-04-11T21:16:06Z |
| format | Article |
| id | doaj.art-d486c8f6dcec48fca2f471230098bdad |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T21:16:06Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d486c8f6dcec48fca2f471230098bdad2022-12-22T04:02:49ZengElsevieriScience2589-00422022-09-01259105028Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis modelAnne Meyer-Miner0Jenica L.M. Van Gennip1Katrin Henke2Matthew P. Harris3Brian Ciruna4Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, The University of Toronto, Toronto, ON M5S 1A8, CanadaProgram in Developmental & Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, The University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Orthopedic Research, Boston Children’s Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Orthopaedics and Department of Human Genetics, Emory University, Atlanta, GA 30322, USADepartment of Orthopedic Research, Boston Children’s Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02115, USAProgram in Developmental & Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, The University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding authorSummary: Idiopathic 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 zebrafish katnb1 mutants 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.http://www.sciencedirect.com/science/article/pii/S2589004222013001Molecular geneticsMolecular biology experimental approachModel organism |
| spellingShingle | Anne Meyer-Miner Jenica L.M. Van Gennip Katrin Henke Matthew P. Harris Brian Ciruna Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model iScience Molecular genetics Molecular biology experimental approach Model organism |
| title | Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model |
| title_full | Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model |
| title_fullStr | Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model |
| title_full_unstemmed | Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model |
| title_short | Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model |
| title_sort | resolving primary pathomechanisms driving idiopathic like spinal curvature using a new katnb1 scoliosis model |
| topic | Molecular genetics Molecular biology experimental approach Model organism |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222013001 |
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