In aging populations of the United States and elsewhere, spinal deformity and bone fragility are two common conditions that threaten quality of life. To clinically address these health concerns requires a clear understanding of bone development. Fibrillar collagens are scaffolds for bone deposition and remodeling and promote bone regeneration in vitro. We identified the type XXVII collagen gene, col27a1 that encodes a fibrillar collagen expressed in human developing cartilage. Preliminary studies in zebrafish indicate that col27a1 is expressed in the notochord during early development and in the cartilage anlagen of bone. Inhibition of col27a1 mRNA translation results in a late scoliosis phenotypein mildly affected embryos and defective somite development and loss of tail elongation in severely affected embryos. I hypothesize that knockdown of col27a1 during embryonic development alters the ultrastructural organization of the notochord, resulting in adult scoliosis. I will examine early notochord development and determine the progression of pathogenesis through adulthood. I will also determine if other notochord-specific genes are abnormally regulated in affected fish and identify ultrastructural changes in the mature vertebral column responsible for spinal deformation. This study will provide a foundation for future translational applications by testing the role of col27a1 in susceptibility to scoliosis and by exploring the critical link between early developmental processes and late-onset dysmorphogenesis. Relevance: Spinal deformity is a common condition in aging adults, but our understanding of the mechanisms involved in development of these conditions is limited. This study will investigate a genetic mechanism involved in development degenerative scoliosis, providing a basis for design of treatments targeting scoliosis and related conditions.
| Christiansen, Helena E; Schwarze, Ulrike; Pyott, Shawna M et al. (2010) Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet 86:389-98 |
| Christiansen, Helena E; Lang, Michael R; Pace, James M et al. (2009) Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth. PLoS One 4:e8481 |
