Biology subjects

Godivier, J.

Publications and source records attributed to Godivier, J..

3 recordsLinked to original sources

bioRxiv2023

Cyclical compression loading is the dominant mechanoregulator of synovial joint morphogenesis

Mechanical stimuli arising from fetal movements are critical factors underlying joint growth. Abnormal fetal movements negatively affect joint shape features with important implications for joint function and health, but the mechanisms by which mechanical forces due to fetal movements influence joint growth are still unclear. In this research, we integrated cell-level data into a novel mechanobiological model of zebrafish jaw joint morphogenesis to identify links between the mechanical stimuli arising from movement and patterns of growth. Larval zebrafish jaw joint growth patterns were quantified from tracked cell-data at several successive developmental stages in the presence or absence of movements. Pharmacological immobilisation, prior to the onset of jaw movements, resulted in growth rate decreases which were stronger along the ventrodorsal axis. Simulations of joint morphogenesis, based on the quantified cell-level data and which integrated mechanical stimuli arising from simulated jaw movements, were used to test hypotheses relating specific mechanical stimuli with the local changes in size and shape. Different types of mechanical stimulation were incorporated into the simulation to provide the mechanoregulated component on growth in addition to the baseline (non mechanoregulated) growth which occurs in the immobilised animals. We found that the magnitude of compression experienced during joint motion when included as the stimulus for mechanoregulated growth could not predict the real, normally loaded shaped joints. However, when the dynamic changes caused by the application of cyclical compression was implemented as the stimulus for mechanoregulated growth, the sizes and shapes of joints were correctly simulated. We conclude therefore that the cyclical application of compression loading due to the dynamic nature of fetal movements underlies the mechanoregulation of prenatal joint morphogenesis. Our results provide a fundamental advance in our understanding of mechanoregulation of the developing joint and increase our understanding of the origins of conditions such as hip dysplasia and arthrogryposis. Author summaryThe mechanical forces caused by fetal movements are important for normal development of the skeleton, and in particular for joint shape. Several common developmental musculoskeletal conditions such as developmental dysplasia of the hip and arthrogryposis are associated with reduced or restricted fetal movements. Paediatric joint malformations impair joint function and can be debilitating. To understand the origins of such conditions, it is essential to understand how the mechanical forces arising from movements influence joint growth and shape. In this research, we used a computational model of joint growth applied to the zebrafish jaw joint to study the impact of fetal movements on joint growth and shape. We find that the cyclical application of compression loading is critical to the normal growth and shape of the developing joint. Our findings implicate that dynamic compression must be targeted when developing strategies for the treatment of musculoskeletal conditions through targeted physiotherapy.

developmental biology↗

bioRxiv2022

Growth orientations, rather than heterogeneous growth rates, dominate jaw joint morphogenesis in the larval zebrafish

In early limb embryogenesis, synovial joints acquire specific shapes which determine joint motion and function. The process by which the opposing cartilaginous joint surfaces are moulded into reciprocal and interlocking shapes, called joint morphogenesis, is one of the least understood aspect of joint formation and the cell-level dynamics underlying it are yet to be unravelled. In this research, we quantified key cellular dynamics involved in growth and morphogenesis of the zebrafish jaw joint and synthesised them in a predictive computational simulation of joint development. Cells in larval zebrafish jaw joints labelled with cartilage markers were tracked over a forty-eight hour time window using confocal imaging. Changes in distance and angle between adjacent cell centroids resulting from cell rearrangement, volume expansion and extracellular matrix (ECM) deposition were measured and used to calculate the rate and direction of local tissue deformations. We observed spatially and temporally heterogeneous growth patterns with marked anisotropy over the developmental period assessed. There was notably elevated growth at the level of the retroarticular process of the Meckels cartilage, a feature known to undergo pronounced shape changes during zebrafish development. Analysis of cell dynamics indicated a dominant role for cell volume expansion in growth, with minor influences from ECM volume increases and cell intercalation. Cell proliferation in the joint was minimal over the timeframe of interest. Synthesising the dynamic cell data into a finite element model of jaw joint development resulted in accurate shape predictions. Our biofidelic computational simulation demonstrated that zebrafish jaw joint growth can be reasonably approximated based on cell positional information over time, where cell positional information derives mainly from cell orientation and cell volume expansion. By modifying the input parameters of the simulation, we were able to assess the relative contributions of heterogeneous growth rates and of growth orientation. The use of uniform rather than heterogeneous growth rates only minorly impacted the shape predictions whereas isotropic growth fields resulted in altered shape predictions. The simulation results suggest that growth anisotropy is the dominant influence on joint growth and morphogenesis. This study addresses the gap of the cellular processes underlying joint morphogenesis, with implications for understanding the aetiology of developmental joint disorders such as developmental dysplasia of the hip and arthrogryposis.

developmental biology↗

bioRxiv2020

Exposure to hypergravity during development leads to altered cartilage material properties and strain distribution in zebrafish.

Terrestrial vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, the effects of shorter exposures to increased gravitational fields are less well characterized. Here, we exposed zebrafish to 3 and 6g hypergravity from 3-5 days post fertilisation, when key events in jaw cartilage morphogenesis occur. We did not observe changes to growth, or morphology of cartilage or muscle. However, we observed altered mechanical properties of jaw cartilages. We model the impact of these material property changes using Finite Element Analysis and show strain distribution in the jaw is altered following hypergravity. In regions of predicted altered strain we observed local changes to chondrocyte morphology, suggesting altered gravity affects chondrocyte maturation, ultimately leading to changes to cartilage structure and function.

physiology↗