Transcriptional Regulation of Vascular Development

Abstract

Vascular development is a highly organized sequence of events that requires the correct spatial and temporal expression of specific sets of genes leading to the development of a primary vascular network. The first step in this process is the differentiation of pluripotent stem cells into endothelial cells. This is followed by endothelial proliferation, migration, and eventual formation of endothelial tubes. Maturation of these primitive tubes into fully developed blood vessels requires the recruitment of surrounding pericytes and their differentiation into vascular smooth muscle cells. Many of the events that occur during vasculogenesis are recapitulated during angiogenesis. Transcription factors have been shown to serve as master switches for regulating a number of developmental processes. Using a candidate gene approach, the genomic regulatory regions required to direct vascular-specific gene expression of several receptor tyrosine kinases that are critical for vasculogenesis have been characterized and some of the transcription factors that are involved in the regulation of these genes have recently been identified. Many of these factors are also involved in the regulation of hematopoiesis and may have overlapping functions in determining hematopoietic and endothelial differentiation. Targeted disruption of other transcription factors that were not previously thought to be involved in vascular development have also been recently shown to play a role in blood vessel development. The purpose of this review is to provide an update on the progress that has been made in our understanding of the transcriptional regulation of vascular development over the past few years.