Craniofacial skeletal defects of adult zebrafish Glypican 4 (knypek) mutants.
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.
Department of Biological Sciences, DePaul University, Chicago, Illinois 60614, USA.
Elizabeth E
EE
LeClair
Stephanie R
SR
Mui
Angela
A
Huang
Jolanta M
JM
Topczewska
Jacek
J
Topczewski
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D002356:Cartilage / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development; D005147:Facial Bones / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development; D055785:Gene Knockdown Techniques; D053673:Glypicans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D012886:Skull / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development; D015027:Zebrafish / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D053673:Glypicans; D029961:Zebrafish Proteins