title: Distinct requirements of wls, wnt9a, wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification.
abstract: Formation of the mandible requires progressive morphologic change, proliferation, differentiation and organization of chondrocytes preceding osteogenesis. The Wnt signaling pathway is involved in regulating bone development and maintenance. Chondrocytes that are fated to become bone require Wnt to polarize and orientate appropriately to initiate the endochondral ossification program. Although the canonical Wnt signaling has been well studied in the context of bone development, the effects of non-canonical Wnt signaling in regulating the timing of cartilage maturation and subsequent bone formation in shaping ventral craniofacial structure is not fully understood.. Here we examined the role of the non-canonical Wnt signaling pathway (wls, gpc4, wnt5b and wnt9a) in regulating zebrafish Meckel's cartilage maturation to the onset of osteogenic differentiation. We found that disruption of wls resulted in a significant loss of craniofacial bone, whereas lack of gpc4, wnt5b and wnt9a resulted in severely delayed endochondral ossification. This study demonstrates the importance of the non-canonical Wnt pathway in regulating coordinated ventral cartilage morphogenesis and ossification.
authors.affiliation: Center for Regenerative Medic ine, Massachusetts General Hospital, Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; School of Medicine, Veterinary and Life Sciences, Glasgow University, UK.
authors.forename: Irving Tc
authors.initials: IT
authors.lastname: Ling
authors.affiliation: Center for Regenerative Medic ine, Massachusetts General Hospital, Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Lucie
authors.initials: L
authors.lastname: Rochard
authors.affiliation: Center for Regenerative Medic ine, Massachusetts General Hospital, Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: cliao@partners.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Liao
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis; D005145:Face; D018507:Gene Expression Regulation, Developmental; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010012:Osteogenesis; D012886:Skull / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D029961:Zebrafish Proteins
keywords: Chondrocyte; Endochondral ossification; Meckel's cartilage; Osteoblast; Wnt; Zebrafish