Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis
Congenital scoliosis (CS) is a type of vertebral malformation for which the etiology remains elusive. The notochord is pivotal for vertebrae development, but its role in CS is still understudied. Here, we generated a zebrafish knockout of ptk7a, a planar cell polarity (PCP) gene that is essential for convergence and extension (C&E) of the notochord, and detected congenital scoliosis-like vertebral malformations (CVMs). Maternal zygotic ptk7a mutants displayed severe C&E defects of the notochord. Excessive apoptosis occurred in the malformed notochord, causing a significantly reduced number of vacuolated cells, and compromising the mechanical properties of the notochord. The latter manifested as a less-stiff extracellular matrix along with a significant reduction in the number of the caveolae and severely loosened intercellular junctions in the vacuolated region. These defects led to focal kinks, abnormal mineralization, and CVMs exclusively at the anterior spine. Loss of function of another PCP gene, vangl2, also revealed excessive apoptosis in the notochord associated with CVMs. This study suggests a new model for CS pathogenesis that is associated with defects in notochord C&E and highlights an essential role of PCP signaling in vertebrae development.
Authors
- Chenjun Shi (ORCID: https://orcid.org/0000-0002-9581-7974)
- Nan Wu (ORCID: https://orcid.org/0000-0002-9429-2889)
- Mingqin Wang (ORCID: https://orcid.org/0009-0001-9445-389X)
- Carl‐Éric Aubin (ORCID: https://orcid.org/0000-0003-2374-008X)
- Josephine T. Tauer (ORCID: https://orcid.org/0000-0002-6079-4653)
- Pierre Drapeau (ORCID: https://orcid.org/0000-0001-9063-0142)
- Nikita Cobetto
- Elke Küster-Schöck (ORCID: https://orcid.org/0000-0002-9487-6948)
- Bettina M. Willie (ORCID: https://orcid.org/0000-0003-2907-3580)
- Meijiang Liao
- Sen Zhao (ORCID: https://orcid.org/0000-0001-9418-4231)
- Jitao Zhang (ORCID: https://orcid.org/0000-0002-6240-0371)
- Marie-Claude Guyot
- Zoha Kibar (ORCID: https://orcid.org/0009-0004-6554-0339)
Institutions
- Academy of Medical Sciences (GB)
- Wayne State University (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Montreal Children's Hospital (CA)
- Peking Union Medical College Hospital (CN)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Polytechnique Montréal (CA)
- McGill University (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- Development
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1242/dev.202829
- Citations
- 2
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Shriners Hospitals for Children
- Canada Foundation for Innovation
- National Institutes of Health
- Natural Sciences and Engineering Research Council of Canada
- Fonds de Recherche du Québec - Santé