Developmental biology of the vascular smooth muscle cell: Building a multilayered vessel wall

The assembly of the vessel wall from its cellular and extracellular matrix components is a critical process in the development and maturation of the c ardiovascular system. However, fundamental questions concerning the origin of vessel wall cells and the mechanisms that regulate their development and differentiation remain unanswered. The initial step of vessel wall morphog enesis is formation of a primary vascular network, comprised of nascent end othelial cell tubes, via the processes of vasculogenesis and angiogenesis, Subsequently, primordial vascular smooth muscle cells (VSMCs) are recruited to the endothelium to form a multilayered vessel wall. During the course o f development and maturation, the VS MC plays diverse roles: it is a biosyn thetic, proliferative, and contractile component of the vessel wall. Althou gh the field of vascular development has blossomed in the past decade, the molecules and mechanisms that regulate this developmental pathway are not w ell defined. The focus of this review is on those facets of VSMC developmen t important for transforming a nascent endothelial tube into a multilayered structure. We discuss the primordial VSMC with particular attention to its purported origins, the components of the extracellular milieu that contrib ute to its development, and the contribution of embryonic hemodynamics to v essel wall assembly.