EMBRYONIC ENDOTHELIAL-CELLS TRANSDIFFERENTIATE INTO MESENCHYMAL CELLSEXPRESSING SMOOTH-MUSCLE ACTINS IN-VIVO AND IN-VITRO

All blood vessels are lined by endothelium and, except for the capilla ries, surrounded by one or more layers of smooth muscle cells. The ori gin of the embryonic vascular smooth muscle cell has until now been de scribed from neural crest and locally differentiating mesenchyme. In t his study, we have substantial evidence that quail embryonic endotheli al cells are competent in the dorsal aorta of the embryo to transdiffe rentiate into subendothelial mesenchymal cells expressing smooth muscl e actins in vivo. At the onset of smooth muscle cell differentiation, QH1-positive endothelial cells were experimentally labeled with a whea t germ agglutinin-colloidal gold marker (WGA-Au). No labeled subendoth elial cells were observed at this time. However, 19 hours after the en dothelial cells had endocytosed, the WGA-Au-labeled subendothelial mes enchymal cells were observed in the aortic wall. Similarly, during the same time period, subendothelial cells that coexpressed the QH1 endot helial marker and a mesenchymal marker, alpha-smooth muscle actin, wer e present. In such cells, QH1 expression was reduced to a cell membran e localization. A similar antigen switch was also observed during endo cardial-mesenchymal transformation in vitro. Our results are the first direct in vivo evidence that embryonic endothelial cells may transdif ferentiate into candidate vascular smooth muscle cells. These data aro use new interpretations of the origin and differentiation of the cells of the vascular wall in normal and diseased vessels.