Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes - PubMed (original) (raw)
Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes
Stephen H Settle Jr et al. Dev Biol. 2003.
Free article
Abstract
Growth/differentiation factors 5, 6, and 7 (GDF5/6/7) represent a distinct subgroup within the bone morphogenetic protein (BMP) family of secreted signaling molecules. Previous studies have shown that the Gdf5 gene is expressed in transverse stripes across developing skeletal elements and is one of the earliest known markers of joint formation during embryonic development. Although null mutations in this gene disrupt formation of some bones and joints in the skeleton, many sites are unaffected. Here, we show that the closely related family members Gdf6 and Gdf7 are expressed in different subsets of developing joints. Inactivation of the Gdf6 gene causes defects in joint, ligament, and cartilage formation at sites distinct from those seen in Gdf5 mutants, including the wrist and ankle, the middle ear, and the coronal suture between bones in the skull. Mice lacking both Gdf5 and Gdf6 show additional defects, including severe reduction or loss of some skeletal elements in the limb, additional fusions between skeletal structures, scoliosis, and altered cartilage in the intervertebral joints of the spinal column. These results show that members of the GDF5/6/7 subgroup are required for normal formation of bones and joints in the limbs, skull, and axial skeleton. The diverse effects on joint development and the different types of joints affected in the mutants suggest that members of the GDF family play a key role in establishing boundaries between many different skeletal elements during normal development. Some of the skeletal defects seen in single or double mutant mice resemble defects seen in human skeletal diseases, which suggests that these genes may be candidates that underlie some forms of carpal/tarsal coalition, conductive deafness, scoliosis, and craniosynostosis.
Similar articles
- Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family.
Storm EE, Kingsley DM. Storm EE, et al. Development. 1996 Dec;122(12):3969-79. doi: 10.1242/dev.122.12.3969. Development. 1996. PMID: 9012517 - GDF5 coordinates bone and joint formation during digit development.
Storm EE, Kingsley DM. Storm EE, et al. Dev Biol. 1999 May 1;209(1):11-27. doi: 10.1006/dbio.1999.9241. Dev Biol. 1999. PMID: 10208739 - Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily.
Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ. Storm EE, et al. Nature. 1994 Apr 14;368(6472):639-43. doi: 10.1038/368639a0. Nature. 1994. PMID: 8145850 - Genetic control of bone and joint formation.
Kingsley DM. Kingsley DM. Novartis Found Symp. 2001;232:213-22; discussion 222-34, 272-82. doi: 10.1002/0470846658.ch15. Novartis Found Symp. 2001. PMID: 11277082 Review. - BMPs, TGFβ, and border security at the interzone.
Lyons KM, Rosen V. Lyons KM, et al. Curr Top Dev Biol. 2019;133:153-170. doi: 10.1016/bs.ctdb.2019.02.001. Epub 2019 Mar 1. Curr Top Dev Biol. 2019. PMID: 30902251 Review.
Cited by
- Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development.
Darbellay F, Ramisch A, Lopez-Delisle L, Kosicki M, Rauseo A, Jouini Z, Visel A, Andrey G. Darbellay F, et al. Nat Commun. 2024 Jun 6;15(1):4820. doi: 10.1038/s41467-024-49203-2. Nat Commun. 2024. PMID: 38844479 Free PMC article. - Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss and Subchondral Bone Damage in a Mechanically Induced Model of Osteoarthritis.
Hollander JM, Goraltchouk A, Liu J, Xu E, Luppino F, McAlindon TE, Zeng L, Seregin A. Hollander JM, et al. Curr Gene Ther. 2024;24(4):331-345. doi: 10.2174/0115665232275532231213063634. Curr Gene Ther. 2024. PMID: 38783531 - Atlantooccipital assimilation associated with combined atlas arch defect: a radiological case report.
Suwannakhan A, Trerattanavong P, Yurasakpong L, Kirisattayakul W, Kruepunga N, Tuntiseranee K, Rumpansuwon K, Senarai T. Suwannakhan A, et al. Anat Cell Biol. 2024 Sep 30;57(3):468-472. doi: 10.5115/acb.23.281. Epub 2024 May 13. Anat Cell Biol. 2024. PMID: 38735652 Free PMC article. - Osteoarthritis as an Enhanceropathy: Gene Regulation in Complex Musculoskeletal Disease.
Roberts JB, Rice SJ. Roberts JB, et al. Curr Rheumatol Rep. 2024 Jun;26(6):222-234. doi: 10.1007/s11926-024-01142-z. Epub 2024 Mar 2. Curr Rheumatol Rep. 2024. PMID: 38430365 Free PMC article. Review. - Transforming growth factor beta signaling and craniofacial development: modeling human diseases in zebrafish.
Fox SC, Waskiewicz AJ. Fox SC, et al. Front Cell Dev Biol. 2024 Feb 7;12:1338070. doi: 10.3389/fcell.2024.1338070. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38385025 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials