How do bones acquire their shapes? Establishing a paradigm for the biology and mechanobiology of morphogenesis of synovial joints.

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Joint shape and function are inextricably linked. Most joints start off as two opposing cartilage surfaces in embryonic development that are moulded into a diverse range of shapes in a process known as morphogenesis. Joint shape has important ramifications for human health, with particular implications for congenital disorders and for aging. Evidence from clinical conditions and from animal models has demonstrated that mechanical forces due to foetal movements play a critical role in the process of moulding joint shapes and affect cellular activity in developing joints. However, we still have a poor understanding of the key drivers and determinants of joint morphogenesis and their final shapes, and in particular of the mechanical modulation of the cellular processes involved. Therefore, the objective of this research is to propose, test and optimise a paradigm for the biology and mechanobiology of shape morphogenesis of synovial joints based upon shape- and cell-level data under normal and abnormal mechanical conditions, using a mechanobiological simulation. This research will provide the first mechanistic model of joint growth and morphogenesis which will enable corroboration of hypotheses relating biophysical stimuli to cellular events leading to growth or changes in shape.This project will focus on the jaw joint of zebrafish in partnership with Chrissy Hammond's lab in Bristol.