Dr Stone is primarily interested in understanding how blood and lymphatic vessels are formed during embryonic development, with the ultimate goal of manipulating their function to treat disease.
The innermost layer of blood and lymphatic vessels is formed by endothelial cells, which are essential for the development and maintenance of all our organs. Despite their importance, we still know relatively little about how they are specified during embryonic development.
During embryogenesis, endothelial cells initially arise from mesoderm. These immature endothelial cells subsequently differentiate to form specialised system (artery / vein / lymphatic) and organ (brain / liver / heart / lung) specific vessel beds. The prevailing view is that following specification from mesoderm, specialisation of endothelial cells is dictated by organ-derived environmental cues.
In this paper, Dr Stone and Dr Stainier show that in addition to local environmental cues, the specialisation of endothelial cells is predetermined by their lineage history. Using genetic lineage tracing in mice, they show that the majority of lymphatic endothelial cells are derived from a subset of the mesoderm known to give rise to skeletal muscle, tendons and cartilage. In contrast, this subset of mesoderm makes a limited contribution to the blood vascular endothelium. By deleting a master regulator of lymphatic endothelial cell differentiation (Prox1), they also show that transition through this lineage is essential for development of the lymphatic vasculature.
Our finding implies that the unique traits of endothelial cells in different vascular beds may be imprinted as they emerge from distinct embryonic lineages. Our ongoing work is investigating the molecular basis of this cellular memory and defining the extent to which lineage history controls endothelial cell heterogeneity in different vascular beds. - Dr Stone
The full paper Paraxial Mesoderm Is the Major Source of Lymphatic Endothelium can be viewed here.