Morphogenesis of the first blood vessels

Abstract

The initial phase of vessel formation is the establishment of nascent endothelial tubes from mesodermal precursor cells. Development of the vascular epithelium is examined using the transcription factor TAL1 as a marker of endothelial precursor cells (angioblasts), and a functional assay based on intact, whole-mounted quail embryos. Experimental studies examining the role(s) of integrins and vascular endothelial growth factor (VEGF) establish that integrin-mediated cell adhesion is necessary for normal endothelial tube formation and that stimulation of embryonic endothelial cells with exogenous VEGF results in a massive "fusion" of vessels and the obliteration of normally avascular zones. The second phase of vessel morphogenesis is assembly of the vessel wall. To understand the process by which mesenchyme gives rise to vascular smooth muscle, a novel monoclonal antibody, 1E12, that recognizes smooth muscle precursor cells was used. Additionally, development of the vessel wall was examined using the expression fo extracellular matrix proteins as markers. Comparison of labeling patterns of 1E12 and the extracellular matrix molecules fibulin-1 and fibrillin-2 indicate vessel wall heterogeneity at the earliest stages of development; thus smooth muscle cell diversity is manifested during the differentiation and assembly of the vessel wall. From these studies it is postulated that the extracellular matrix composition of the vessel wall may prove to be the best marker of smooth muscle diversity. The data are discussed in the context of recent work by others, especially provocative new studies suggesting an endothelial origin for vascular smooth muscle cells. Also discussed is recent work that provides clues to the mechanism of vascular smooth muscle induction and recruitment. Based on these findings, vascular smooth muscle cells can be thought of as existing along a continuum of phenotypes. This spectrum varies from mainly matrix-producing cells to primarily contractile cells; thus no one cell type typifies vascular smooth muscle. This view of the smooth muscle cell is considered in terms of a contrasting opinion that views smooth muscle cell as existing in either a synthetic or proliferative state.