title: The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signaling.
abstract: The ability of mature organisms to stabilize phenotypes has enormous selective advantage across all phyla, but the mechanisms have been largely unexplored. Individuals with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of progressive heterotopic ossification, undergo a pathological metamorphosis in which one normal tissue is transformed into another through a highly regulated process of tissue destruction and phenotype reassignment. This disabling metamorphosis is mediated by the FOP metamorphogene, which encodes a mutant bone morphogenetic protein (BMP) type I receptor that exhibits mild constitutive activity during development and severe episodic dysregulation postnatally. The discovery of the FOP metamorphogene reveals a highly conserved target for drug development and identifies a fundamental defect in the BMP signaling pathway that when triggered by injury and inflammation transforms one tissue into another.
authors.affiliation: Department of Orthopaedic Surgery, The Center for Research in FOP & Related Disorders, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. frederick.kaplan@uphs.upenn.edu
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pignolo
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000502:physiology; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology / Q000293:injuries; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009221:Myositis Ossificans / Q000150:complications / Q000235:genetics* / Q000628:therapy; D009999:Ossification, Heterotopic / Q000209:etiology / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I