The Intestinal Mesoderm: Investigation of its Development and Potential

Abstract

The mesodermal germ layer contributes many cell types that comprise the coelomic organs during embryogenesis. One such mesodermally derived cell type is the mesothelium, which is an epithelial sheet that covers organs in the coelomic cavity and is involved in development of the vascular system. The development of the mesothelium has been well characterized in the heart. The heart mesothelial progenitor cells, the proepicardium (PE), develop independently, migrate onto and over the heart to form the epicardium, and then undergo epithelial-mesenchymal transition (EMT) to give rise to the cells of the coronary blood vessels. Conversely, the progenitors of gut mesothelium are currently unknown, but studies have shown that these cells also undergo EMT and serve as a major source of vascular smooth muscle cells for the gut tube in development. These findings suggest a conserved mechanism of development within both the gut and heart mesothelium. Thus, we hypothesized that the gut mesothelium possesses a similar developmental potential to the epicardium, including: 1) mechanisms by which the progenitor cells develop, and 2) that mesothelial cells have the same potential to incorporate into all mesothelial tissues and contribute cells to any organ when surgically interchanged. First, immunohistochemical studies of avian mesodermal development were conducted to determine the developmental timing and location of mesothelial cells in the gut. To test the above hypotheses direct lineage tracing techniques and a chick-quail chimera system were employed to determine the origin of gut mesothelium. Surprisingly, the gut mesothelium did not develop from an external cell population, but instead from resident cells in the splanchnic mesoderm. However, transplantation of gut mesothelium into the pericardial cavity revealed successful incorporation into epicardium, contribution of smooth muscle cells to vessels, and fibroblasts to the heart. Conversely, PE and epicardial cells transplanted to the peritoneal cavity did not display this same interchangeable capacity. These studies demonstrate that the origins of heart and gut mesothelia differ and only the gut mesothelial cells possess pliable characteristics.