Publication Date
4-30-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2310283121
PMID
38669183
PMCID
PMC11067467
PubMedCentral® Posted Date
4-26-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Zebrafish, Humans, Mice, Cell Polarity, Membrane Proteins, Spine, Zebrafish Proteins, Scoliosis, Wnt Signaling Pathway, Genetic Predisposition to Disease, Nerve Tissue Proteins, Intracellular Signaling Peptides and Proteins, Female, Carrier Proteins, congenital vertebral malformation, congenital scoliosis, somite, VANGL1/2, planar cell polarity (PCP)
Abstract
Congenital scoliosis (CS) is the most common congenital spinal disorder caused by congenital vertebral malformations (CVMs), influenced by genetic and environmental factors and exhibiting diverse clinical presentations. Here, we identified the critical roles of Vangl1 and Vangl2, two core components in the Wnt/planar cell polarity (Wnt/PCP) signaling pathway, in vertebral development and in predisposition to CVMs in CS patients. We found that in Vangl mutant mouse models, the CVMs present in a Vangl gene dose- and gestational hypoxia-dependent manner. Our studies reveal a complex etiology of CS and its association with Wnt/PCP signaling.
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