title: Roles of the primary cilium component Polaris in synchondrosis development.
abstract: Primary cilia regulate several developmental processes and mediate hedgehog signaling. To study their roles in cranial base development, we created conditional mouse mutants deficient in Polaris, a critical primary cilium component, in cartilage. Mutant post-natal cranial bases were deformed, and their synchondrosis growth plates were disorganized. Expression of Indian hedgehog, Patched-1, collagen X, and MMP-13 was reduced and accompanied by decreases in endochondral bone. Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by excessive Patched-1 expression, suggesting that Ihh distribution was wider and responsible for such excessive response. Indeed, expression of heparan sulfate proteoglycans (HS-PGs), normally involved in restricting hedgehog distribution, was barely detectable in mutant synchondroses. Analyses of the data provides further evidence for the essential roles of primary cilia and hedgehog signaling in cranial base development and chondrocyte maturation, and point to a close interdependence between cilia and HS-PGs to delimit targets of hedgehog action in synchondroses.
authors: Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, 1015 Walnut Street, Curtis Building, Room 501, Philadelphia, PA 19107, USA.
authors: T
authors: T
authors: Ochiai
authors: M
authors: M
authors: Nagayama
authors: T
authors: T
authors: Nakamura
authors: T
authors: T
authors: Morrison
authors: D
authors: D
authors: Pilchak
authors: N
authors: N
authors: Kondo
authors: H
authors: H
authors: Hasegawa
authors: B
authors: B
authors: Song
authors: R
authors: R
authors: Serra
authors: M
authors: M
authors: Pacifici
authors: E
authors: E
authors: Koyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D019902:Chondrocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D002923:Cilia / Q000737:chemistry; D024121:Collagen Type X / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis; D007124:Immunoenzyme Techniques; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015398:Signal Transduction; D019291:Skull Base / Q000166:cytology / Q000254:growth & development*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D024121:Collagen Type X; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins; C514061:ihh protein, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse