Location Monash University, Australian Regenerative Medicine Institute

Characterising unilateral catch-up growth after insult-induced asymmetries in the developing long bones

The extracellular matrix-associated Connective Tissue Growth Factor (CTGF) is considered a double-edged sword during organ development and repair, as it can promote organ fibrosis and scarring but also wound healing. The developing bones produce CTGF, but its role during normal development and repair is not completely understood. In the Rosello-Diez lab we have developed mouse genetic models with which we can misexpress the gene of interest in the left-limb skeletal elements, such that the right limb remains as an internal control. Using this strategy, we have observed that misexpression of Ctgf in one third of the cells that compose the cartilage (chondrocytes) leads to a very severe bone shortening, with almost complete disappearance of one of the regions of the growing cartilage. Interestingly, the phenotype is transient, such that the cartilage eventually recovers its normal architecture and growth resumes. In this project, the student will perform histological analysis (immunohistochemistry, in situ hybridization, etc), skeletal preparations and dynamic histomorphometry to characterise the catch-up growth response at different time points. We will also express Ctgf from different tissues to distinguish between bone-intrinsic and -extrinsic effect of Ctgf. The elucidation of the complex roles of this growth factor, and the mechanisms underlying catch-up growth could have far-reaching implications in regenerative medicine. An alternative/complementary project will use a model of transient unilateral cell death affecting only some of the cells that drive bone growth. Preliminary evidence suggest that the injured limb can catch-up quite rapidly, a response that will be analysed at the cellular and molecular level. These projects could easily evolve towards a PhD project.


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