A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations

摘要

During animal development, the ribs grow from the back of the embryo around towards the chest. In fish, these bones simply terminate. Yet in land animals, cartilage forms at the end of the rib where it connects to the breastbone, or sternum. This encloses the chest cavity. Fogel, Lakeland et al. have now asked how the progenitor cells that develop into the ribs form these two skeletal elements – the bone element and the cartilage element – in land animals. Their approach involved genetic analysis in mice and a simple computing model. It revealed that two elements could form if the progenitor cells decide which element they will belong to based on the concentration of the diffusible protein called Hedgehog. This protein controls many aspects of animal development, and higher concentrations seem to bias the cells in a developing rib toward belonging to the bone element. Fogel, Lakeland et al. propose that this decision is locked-in early, before the rib grows outward and becomes more refined. An analysis using this simple model reproduces all the basic observations seen in the experiments with mice. The model also explains how processes like cell division and cell death control the growth of developing skeletal elements. These modeling techniques can be applied to many fields within biology, including research into the causes of birth defects, the mechanisms of tissue repair, and the evolution of skeletal diversity. An advantage to this modeling technique is that it uses only the information in each cell’s local environment to make decisions.