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We previously showed that the <jats:italic>FGFR2<\/jats:italic> mutations in BBDS enhance nuclear and nucleolar localization of the receptor; however, exactly how shifts in subcellular distribution of FGFR2 affect limb development remained unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Targeted expression of the BBDS mutations in the lateral plate mesoderm of the developing chick induced angulated hindlimbs, a hallmark feature of the disease. Whole\u2010mount analysis of the underlying skeleton revealed bent long bones with shortened bone collars and, in severe cases, dysmorphic epiphyses. Epiphyseal changes were also correlated with joint dislocations and contractures. Histological analysis revealed that bent long bones and joint defects were closely associated with irregularities in skeletal muscle patterning and tendon\u2010to\u2010bone attachment. The spectrum of limb phenotypes induced by the BBDS mutations were recapitulated by targeted expression of wild\u2010type FGFR2 appended with nuclear and nucleolar localization signals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that the bent long bones in BBDS arise from disruptions in musculoskeletal integration and that increased nuclear and nucleolar localization of FGFR2 plays a mechanistic role in the disease phenotype. 248:233\u2010246, 2019. \u00a9 2018 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.9","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T02:12:00Z","timestamp":1546999920000},"page":"233-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nuclear FGFR2 regulates musculoskeletal integration within the developing limb"],"prefix":"10.1002","volume":"248","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3759-2268","authenticated-orcid":false,"given":"Joanna E.","family":"Salva","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry University of Southern California  Los Angeles California"},{"name":"Department of Biochemistry and Molecular Medicine, Keck School of Medicine University of Southern California  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan R.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry University of Southern California  Los Angeles California"},{"name":"Department of Biochemistry and Molecular Medicine, Keck School of Medicine University of Southern California  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor 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