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The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416\u2013429.","DOI":"10.1038\/nrm3598"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2 Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059\u20133087.","DOI":"10.1101\/gad.938601"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3 Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev. 2008;22(18):2454\u20132472.","DOI":"10.1101\/gad.1693608"},{"key":"4","doi-asserted-by":"publisher","unstructured":"4 Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G, Hogan BL. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development. 1997;124(1):53\u201363.","DOI":"10.1242\/dev.124.1.53"},{"key":"5","doi-asserted-by":"publisher","unstructured":"5 Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BL. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development. 1997;124(23):4867\u20134878.","DOI":"10.1242\/dev.124.23.4867"},{"key":"6","doi-asserted-by":"publisher","unstructured":"6 Chuang PT, McMahon AP. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature. 1999;397(6720):617\u2013621.","DOI":"10.1038\/17611"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7 Bishop B, Aricescu AR, Harlos K, O\u2019Callaghan CA, Jones EY, Siebold C. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP. Nat Struct Mol Biol. 2009;16(7):698\u2013703.","DOI":"10.1038\/nsmb.1607"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8 Holtz AM, Griffiths SC, Davis SJ, Bishop B, Siebold C, Allen BL. Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function. 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Developmental regulation of the growth plate. Nature. 2003;423(6937):332\u2013336.","DOI":"10.1038\/nature01657"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25 Nilsson O, Baron J. Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusion. Trends Endocrinol Metab. 2004;15(8):370\u2013374.","DOI":"10.1016\/j.tem.2004.08.004"},{"key":"26","doi-asserted-by":"publisher","unstructured":"26 Mak KK, Chen MH, Day TF, Chuang PT, Yang Y. Wnt\/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development. 2006;133(18):3695\u20133707.","DOI":"10.1242\/dev.02546"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27 Haraguchi R, Kitazawa R, Imai Y, Kitazawa S. Growth plate-derived hedgehog-signal-responsive cells provide skeletal tissue components in growing bone. 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