Developmental genetics of the zebrafish skeleton

Osteoarthritis is a major obstacle to work productivity and quality of life for many Canadians, affecting over 10% of the general population and 15% of Saskatchewanians, with the elderly increasingly affected (>40% of Canadians over 65 years old). At the cellular and molecular level, osteoarthritis involves two main defects: 1) degradation of sugar-coated proteins (proteoglycans) in the cartilage that protects bones at the joints, and 2) changes to gene expression in the cells (chondrocytes) that maintain cartilage. For over 15 years, our vertebrate cousin, the zebrafish, has been a widely-accepted research model of human development and disease. Recently, I identified zebrafish with mutations in cartilage proteoglycan production and showed that loss of proteoglycans itself causes changes to chondrocyte gene expression. This novel experimental system provides a fresh, unexplored avenue for understanding and eventually treating osteoarthritis. This project studies the molecular mechanism by which proteoglycans change chondrocyte gene expression, hypothesizing that proteoglycans in the cartilage modulate the biological activity of growth factors, specifically bone morphogenetic proteins (BMPs), which in turn alter chondrocyte gene expression. To test this hypothesis, this project uses many powerful experimental tools available in zebrafish (e.g., mutants, transgenics, and embryonic injections) to manipulate the proteoglycan levels in cartilage matrix and/or BMP activity, and measure the effects on chondrocyte gene expression.

Faculty Supervisor:

Brian Eames








University of Saskatchewan



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