As the developing mammalian embryo expands beyond a small mass of cells, it acquires a need to establish circulation in order to facilitate communication among different parts of the embryo. It also must establish a mechanism for nutrition and oxygenation once simple diffusion becomes a limiting mechanism. These requirements provide a rationale for why the cardiovascular system is the first to function during mammalian development. An analysis of vascular development therefore provides a paradigm for understanding the general principles of organ development in mammals. Practical reasons also exist to elucidate the mechanisms by which blood vessels form. It is clear that defective vascular development contributes to a number of congenital conditions in humans, from hereditary angiomas to more complicated developmental syndromes. In addition, we now know that many pathological events in adults follow rules that resemble developmental events, such that understanding the latter can in form how we approach the former. In this chapter, we briefly review the field of vascular development from an historical perspective, after which the key steps in mammalian endothelial differentiation will be considered, with a focus on the molecular and cellular events that underlie the principles of developmental blood vessel formation.

HISTORICAL OVERVIEW

Consistent with its central importance in embryonic development, the history of research into vascular development is populated with seminal histologists such as Wilhelm His and Florence Sabin (see Chapter 1). Ideas about endothelial origin followed shortly after the development of histology and cell biology as fields of study.