Limb development is regulated by feedback between the tissue-scale mechanics and cellular decisions–migration, contraction, division, and death–implemented through gene-regulatory networks. The dynamically changing states of these cellular networks reflect the decisions being made. To integrate these interactions across 3 scales: genes, cells, and tissues, we develop a 3D cell-based model in...
In the early embryo an intracellular oscillator known as the segmentation clock patterns the somites, blocks of mesoderm that give rise to vertebrae and skeletal muscle. Clock oscillations are coupled between cells of the pre-somitic mesoderm (PSM) via notch-delta signalling, synchronising differentiation of PSM cells into somites. While this is happening, PSM cells are rearranging and...
Morphogens are intercellular signalling molecules that provide spatial information to cells in developing tissues by establishing long-range concentration gradients. Measurements of morphogen diffusivity vary considerably depending on the experimental approach, and these discrepancies have been used to question diffusion as a viable mechanism for morphogen gradient formation. Using...
Radial dysplasia (RD) is a musculoskeletal disorder in which the anatomical structure of the forelimb is fundamentally altered - in extreme cases the radius bone is missing, along with a number of muscles. RD is a disorder of later development, that manifests through changes in the extracellular matrix (ECM) deposition behaviour of a population of fibroblast precursors. As muscle cells follow...
During embryonic development, cells differentiate and self-organise with remarkable robustness to form complex tissue structures. These processes arise from tightly coupled interactions between morphogen transport, biochemical signalling, cellular dynamics, and tissue mechanics. Despite significant progress, how these mechanisms act together to drive developmental patterning and morphogenesis...
