Craniofacial skeletal defects of adult zebrafish Glypican 4 (knypek) mutants

Dev Dyn. 2009 Oct;238(10):2550-63. doi: 10.1002/dvdy.22086.


The heparan sulfate proteoglycan Glypican 4 (Gpc4) is part of the Wnt/planar cell polarity pathway, which is required for convergence and extension during zebrafish gastrulation. To observe Glypican 4-deficient phenotypes at later stages, we rescued gpc4(-/-) (knypek) homozygotes and raised them for more than one year. Adult mutants showed diverse cranial malformations of both dermal and endochondral bones, ranging from shortening of the rostral-most skull to loss of the symplectic. Additionally, the adult palatoquadrate cartilage was disorganized, with abnormal chondrocyte orientation. To understand how the palatoquadrate cartilage normally develops, we examined a juvenile series of wild type and mutant specimens. This identified two novel domains of elongated chondrocytes in the larval palatoquadrate, which normally form prior to endochondral ossification. In contrast, gpc4(-/-) larvae never form these domains, suggesting a failure of chondrocyte orientation, though not differentiation. Our findings implicate Gpc4 in the regulation of zebrafish cartilage and bone morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning*
  • Cartilage* / abnormalities
  • Cartilage* / anatomy & histology
  • Cartilage* / growth & development
  • Facial Bones* / abnormalities
  • Facial Bones* / anatomy & histology
  • Facial Bones* / growth & development
  • Gene Knockdown Techniques
  • Glypicans / genetics
  • Glypicans / metabolism*
  • Humans
  • Phenotype
  • Skull* / abnormalities
  • Skull* / anatomy & histology
  • Skull* / growth & development
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • Zebrafish* / abnormalities
  • Zebrafish* / anatomy & histology
  • Zebrafish* / growth & development


  • Glypicans
  • Zebrafish Proteins