Growth differentiation factor 6 (GDF6) is a regulatory protein associated with growth and differentiation of developing embryos. GDF6 is encoded by the GDF6 gene. It is a member the transforming growth factor beta superfamily which is a group of proteins involved in early regulation of cell growth and development. GDF6 has been shown to play an important role in the patterning of the epidermis and bone and joint formation. GDF6 induces genes related to the development of the epidermis and can bind directly to noggin, a gene that controls neural development, to block its effect. GDF6 interacts with bone morphogenetic proteins (BMPs) to form heterodimers that may work to regulate neural induction and patterning in developing embryos. By developing a GDF6 “knockout” model, scientists repressed expression of GDF6 in developing mice embryos. Through this experiment, the scientists were able to directly link GDF6 with several skull and vertebral joint disorders, such as scoliosis and chondrodysplasia, Grebe type.
^ abcChang C, Hemmati-Brivanlou A (August 1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development126 (15): 3347–57. PMID10393114.
^ abSettle SH, Rountree RB, Sinha A, Thacker A, Higgins K, Kingsley DM (February 2003). "Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes". Dev. Biol.254 (1): 116–30. doi:10.1016/S0012-1606(02)00022-2. PMID12606286.
Mazerbourg S, Sangkuhl K, Luo CW, et al. (2005). "Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses". J. Biol. Chem.280 (37): 32122–32. doi:10.1074/jbc.M504629200. PMID16049014.
Storm EE, Huynh TV, Copeland NG, et al. (1994). "Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily". Nature368 (6472): 639–43. doi:10.1038/368639a0. PMID8145850.
Erlacher L, McCartney J, Piek E, et al. (1998). "Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis". J. Bone Miner. Res.13 (3): 383–92. doi:10.1359/jbmr.1918.104.22.1683. PMID9525338.
Tassabehji M, Fang ZM, Hilton EN, et al. (2008). "Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome". Hum. Mutat.29 (8): 1017–27. doi:10.1002/humu.20741. PMID18425797.
Tomaski SM, Zalzal GH (1999). "In vitro regulation of expression of cartilage-derived morphogenetic proteins by growth hormone and insulinlike growth factor 1 in the bovine cricoid chondrocyte". Arch. Otolaryngol. Head Neck Surg.125 (8): 901–6. doi:10.1001/archotol.125.8.901. PMID10448738.
Asai-Coakwell M, French CR, Ye M, et al. (2009). "Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes". Hum. Mol. Genet.18 (6): 1110–21. doi:10.1093/hmg/ddp008. PMID19129173.
Bobacz K, Gruber R, Soleiman A, et al. (2002). "Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis". Osteoarthr. Cartil.10 (5): 394–401. doi:10.1053/joca.2002.0522. PMID12027540.
Chang SC, Hoang B, Thomas JT, et al. (1994). "Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development". J. Biol. Chem.269 (45): 28227–34. PMID7961761.