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

• Published in: Developmental dynamics Vol. 238; no. 10; pp. 2550 - 2563
• Main Authors: LeClair, Elizabeth E., Mui, Stephanie R., Huang, Angela, Topczewska, Jolanta M., Topczewski, Jacek
• Format: Journal Article
• Language: English
• Published: New York Wiley‐Liss, Inc 01.10.2009
• Subjects: Animals; Animals, Genetically Modified; Body Patterning; bone; cartilage; Cartilage - abnormalities; Cartilage - anatomy & histology; Cartilage - growth & development; craniofacial; Facial Bones - abnormalities; Facial Bones - anatomy & histology; Facial Bones - growth & development; Gene Knockdown Techniques; glypican; Glypicans - genetics; Glypicans - metabolism; Humans; jaw; knypek; morphometrics; Phenotype; skull; Skull - abnormalities; Skull - anatomy & histology; Skull - growth & development; zebrafish; Zebrafish - abnormalities; Zebrafish - anatomy & histology; Zebrafish - growth & development; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1058-8388; 1097-0177
• 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. Developmental Dynamics 238:2550–2563, 2009. © 2009 Wiley‐Liss, Inc.