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.
LeClair
Elizabeth E
EE
Department of Biological Sciences, DePaul University, Chicago, Illinois 60614, USA.
Mui
Stephanie R
SR
Huang
Angela
A
Topczewska
Jolanta M
JM
Topczewski
Jacek
J
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