Connecting the cells: vascular differentiation via homeobox genes and extracellular matrix in the distal lung.

Abstract

Although tremendous strides have been made in understanding how blood vessels form in the embryo, little is known about the role of individual genes during vasculogenesis or angiogenesis. Questions remain about transcriptional regulators of blood vessel formation or whether there are differences in embryonic gene expression in distinct vascular beds. An article in this issue of Circulation Research by Ihida-Stansbury et al1 may provide clues to these enigmatic questions. These authors explored the relationship between the paired related homeobox gene, Prx1 , one of its downstream targets, tenascin-C (TN-C), and endothelial specification during vascular development in the distal lung mesoderm. Pulmonary vascular development represents a unique system of blood vessel formation. First, angiogenesis and vasculogenesis proceed independently in the proximal and distal portions of the growing lung buds. Proximally, the pulmonary arteries grow into the lung bud by angiogenic sprouting from the dorsal aorta or aortic sac.2 Distally, the foregut mesoderm organizes into a capillary bed by vasculogenesis. The distal and proximal beds join to form the complete network of arteries, veins, and capillaries. Second, interaction between the forming airways and surrounding mesenchyme is essential for inducing vasculogenesis as well as specialization of alveolar epithelial cells. Thus, in addition to angiogenic outgrowth from the aorta into the proximal lung, all vascular cell types in the distal lung are derived from foregut mesoderm through induction from the airways. Homeobox (Hox) genes encode transcription factors that are master regulators of patterning in development.3 These ancient genes control diversification of segments along the anteroposterior axis of all animals. Common to all of the proteins encoded by members of the Hox gene family is a 60 amino acid DNA binding homeodomain. The finding that Hox genes encoded transcription factors led to the idea …