title: A role of glypican4 and wnt5b in chondrocyte stacking underlying craniofacial cartilage morphogenesis.
abstract: The Wnt/Planar Cell Polarity (PCP) pathway controls cell morphology and behavior during animal development. Several zebrafish mutants were identified as having perturbed Wnt/PCP signaling. Many of these mutants have defects in craniofacial formation. To better understand the role that Wnt/PCP plays in craniofacial development we set out to identify which of the mutants, known to be associated with the Wnt/PCP pathway, perturb head cartilage formation by disrupting chondrocyte morphology. Here we demonstrate that while vang-like 2 (vangl2), wnt11 and scribbled (scrib) mutants have severe craniofacial morphogenesis defects they do not display the chondrocyte stacking and intercalation problems seen in glypican 4 (gpc4) and wnt5b mutants. The function of Gpc4 or Wnt5b appears to be important for chondrocyte organization, as the neural crest in both mutants is specified, undergoes migration, and differentiates into the same number of cells to compose the craniofacial cartilage elements. We demonstrate that Gpc4 activity is required cell autonomously in the chondrocytes and that the phenotype of single heterozygous mutants is slightly enhanced in embryos double heterozygous for wnt5b and gpc4. This data suggests a novel mechanism for Wnt5b and Gpc4 regulation of chondrocyte behavior that is independent of the core Wnt/PCP molecules and differs from their collaborative action of controlling cell movements during gastrulation.
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Stanley Manne Children's Research Institute, Chicago, IL 60611, USA; Ripon College, Department of Biology, 300 Seward St., Ripon, WI 54971, USA. Electronic address: sissonb@ripon.edu.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Sisson
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Stanley Manne Children's Research Institute, Chicago, IL 60611, USA; Loyola University Chicago, Department of Biology, Quinlan 222, 1032 W. Sheridan Rd., Chicago, IL 60660, USA. Electronic address: rdale1@luc.edu.
authors.forename: Rodney M
authors.initials: RM
authors.lastname: Dale
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Stanley Manne Children's Research Institute, Chicago, IL 60611, USA. Electronic address: stephanie.r.mui@gmail.com.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Mui
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Stanley Manne Children's Research Institute, Chicago, IL 60611, USA; Northwestern University Feinberg School of Medicine, Department of Surgery, Stanley Manne Children's Research Institute, 225 East Chicago Avenue, Box 93, Chicago, IL 60611, USA. Electronic address: j-topczewska@northwestern.edu.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Topczewska
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Stanley Manne Children's Research Institute, Chicago, IL 60611, USA. Electronic address: j-topczewski@northwestern.edu.
authors.forename: Jacek
authors.initials: J
authors.lastname: Topczewski
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D048429:Cell Size; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053673:Glypicans / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D000071818:Wnt-5a Protein; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D053673:Glypicans; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C480282:Wnt5a protein, zebrafish; D029961:Zebrafish Proteins
keywords: Growth plate; Wnt/PCP pathway; knypek; pipe tail