Ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease

Madeline Hayes, Xiaochong Gao, Lisa X. Yu, Nandina Paria, R. Mark Henkelman, Carol A. Wise, Brian Ciruna

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Scoliosis is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine. Curvatures caused by malformed vertebrae (congenital scoliosis (CS)) are apparent at birth. Spinal curvatures with no underlying vertebral abnormality (idiopathic scoliosis (IS)) most commonly manifest during adolescence. The genetic and biological mechanisms responsible for IS remain poorly understood due largely to limited experimental models. Here we describe zygotic ptk7 (Zptk7) mutant zebrafish, deficient in a critical regulator of Wnt signalling, as the first genetically defined developmental model of IS. We identify a novel sequence variant within a single IS patient that disrupts PTK7 function, consistent with a role for dysregulated Wnt activity in disease pathogenesis. Furthermore, we demonstrate that embryonic loss-of-gene function in maternal-zygotic ptk7 mutants (MZptk7) leads to vertebral anomalies associated with CS. Our data suggest novel molecular origins of, and genetic links between, congenital and idiopathic forms of disease.

Original languageEnglish (US)
Article number4777
JournalNature Communications
Volume5
DOIs
StatePublished - Sep 3 2014

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Scoliosis
Zebrafish
Musculoskeletal system
curvature
vertebrae
pathogenesis
spine
Genes
regulators
abnormalities
musculoskeletal system
genes
disorders
anomalies
Spine
Spinal Curvatures
Musculoskeletal System
Inborn Genetic Diseases
Molecular Biology
Theoretical Models

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. / Hayes, Madeline; Gao, Xiaochong; Yu, Lisa X.; Paria, Nandina; Henkelman, R. Mark; Wise, Carol A.; Ciruna, Brian.

In: Nature Communications, Vol. 5, 4777, 03.09.2014.

Research output: Contribution to journalArticle

Hayes, Madeline ; Gao, Xiaochong ; Yu, Lisa X. ; Paria, Nandina ; Henkelman, R. Mark ; Wise, Carol A. ; Ciruna, Brian. / Ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. In: Nature Communications. 2014 ; Vol. 5.
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