title: Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.
abstract: During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development.
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Wei
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Bojiang
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Williams
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhargav
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Twishi
authors.initials: T
authors.lastname: Gulati
authors.affiliation: Human Molecular Genetics, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Sarennya
authors.initials: S
authors.lastname: Pathmanandavel
authors.affiliation: Department of Orthopedic Research, Orthopedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Ashish D
authors.initials: AD
authors.lastname: Diwan
mesh_terms: D002356:Cartilage / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism; D055431:Growth Differentiation Factor 6 / Q000378:metabolism*; D006801:Humans; D010012:Osteogenesis; D011509:Proteoglycans / Q000378:metabolism; D013131:Spine / Q000196:embryology* / Q000378:metabolism
chemical_list: C525906:GDF6 protein, human; D055431:Growth Differentiation Factor 6; D011509:Proteoglycans; D003094:Collagen
keywords: BMP13; CDMP2; GDF6; fetal spine; vertebral column