The morphogenesis of synovial joints is essential to the function of the joint, yet the regulatory mechanisms underlying this process remain elusive. In the case of reduced or absent mechanical stimulation, joint cavitation can
fail, with consequences for growth and joint shape. Mechanical stimuli effect a variety of changes to cell activity,
however spatial distributions of stress and activity have not been characterised throughout the joint. Joint morphogenesis is measured through the growth of shape features, which integrates the effects of cell activity on growth
from a multitude of cells, preventing a relationship between growth and cell activity from being characterised. This
thesis aimed (1) to quantify the evolution of stress and shape throughout the joint over morphogenesis, (2) quantify
spatio-temporal variation in cell proliferation throughout the joint over morphogenesis, (3) develop an inference
model of growth to quantify spatial variation in growth throughout the joint.
The thesis studied the development of the knee in chick hind-limb explants, and identified spatio-temporal variation
in shape growth, stress and proliferation that had not been previously characterised. A hypothesis was developed
that while proliferating, cells have a reduced capacity to perform other growth processes, such as matrix production,
but larger cell populations yield more growth at a later time. The inference model developed showed that growth
rates were concentrated in regions of high stress, and provides the opportunity to visualise how the activities of
individual cells contribute to the morphogenesis of a tissue as a whole.
This research provided deeper insight into the role of mechanical loading on joint development, and established
methods to investigate joint morphogenesis with greater precision. This thesis has not only deepened our understanding of the dynamics of morphogenesis, but has created new ways to study organogenesis as a whole.