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.
Original language | English (US) |
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Pages (from-to) | 399-407 |
Number of pages | 9 |
Journal | Cytokine and Growth Factor Reviews |
Volume | 20 |
Issue number | 5-6 |
DOIs | |
State | Published - Oct 2009 |
Keywords
- ACVR1
- Activin-like kinase 2 (ALK2)
- BMP signaling
- Bone morphogenetic protein (BMP) receptor
- Fibrodysplasia ossificans progressiva
- Heterotopic ossification
- Metamorphogene
- Metamorphosis
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Immunology and Allergy
- Immunology
- General Biochemistry, Genetics and Molecular Biology