Life before Nkx2.5: cardiovascular progenitor cells: embryonic origins and development

Development of the heart, like that of other organs, requires the specification of progenitor cell populations that will ultimately form the differentiated cell types of the functional organ. A relatively recent and exciting advance in cardiac research has been the identification of cardiovascular progenitor cells (CPCs), which have the potential to form the major cell types of the heart (cardiomyocytes, smooth muscle, and endothelium/endocardium). This suggests that a common progenitor is responsible for much of heart development and has spurred great interest in use of CPC-like cells for cardiac repair. In this review, CPC development is discussed, with a focus on early events prior to the initiation of cardiac gene expression. In particular, I discuss evidence that CPC fate is established during gastrulation, well before a time when heart development has typically been studied. Pathways regulating CPC specification are examined. The relationship between CPC specification and migration is further discussed. Finally, how CPCs may be related to efforts to promote cardiac development by approaches including reprogramming is discussed.