title: Dysregulation of the BMP-4 signaling pathway in fibrodysplasia ossificans progressiva.
abstract: Identification of gene mutations in Mendelian disorders is often determined by linkage analysis and positional cloning, an approach that is difficult for fibrodysplasia ossificans progressiva (FOP) due to a low reproductive fitness that results in a small number of multigenerational families showing inheritance of the disease. Altered signaling pathways can be investigated as a complementary method to identify the consequences of the mutated gene responsible for FOP and to identify potential therapeutic targets. Candidate signaling pathways for FOP are those that malfunctioning could account for the malformation of the great toes during embryonic development and could explain the postnatal progressive heterotopic endochondral ossification. Signaling pathways that fit these criteria are the BMP signaling pathway and its interacting pathways. A large body of data suggest that the BMP-4 signaling pathway is dysregulated in FOP.
authors.affiliation: University of Pennsylvania School of Medicine, Department of Orthopaedic Surgery, Silverstein Two, 3400 Spruce Street, Philadelphia, PA 19104, USA. frederick.kaplan@uphs.upenn.edu
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fiori
authors.forename: Lourdes Serrano
authors.initials: LS
authors.lastname: DE LA Peña
authors.forename: Jaimo
authors.initials: J
authors.lastname: Ahn
authors.forename: Paul C
authors.initials: PC
authors.lastname: Billings
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
mesh_terms: D000818:Animals; D001846:Bone Development; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D006801:Humans; D009221:Myositis Ossificans / Q000235:genetics / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D052004:Bone Morphogenetic Protein Receptors