**4. Hox genes in vascularity and angiogenesis**

The development of the vascular system involves two processes called vasculogenesis and angiogenesis [42]. During vasculogenesis, angioblasts derived from different sources, including mesodermal embryonic layer or bone marrow, differentiate into endothelial cells and subsequently form a primitive network of tubular structures called blood vessels [43]. Vasculogenesis occurs largely during embryonic development; however, the presence of a population of circulating endothelial progenitor cells (EPCs) derived from the bone marrow in adults strongly suggests that this process may occur in the postnatal period [44]. In contrast, angiogenesis refers to the formation of new blood vessels from preexisting vessels by cell migration and remodeling of the primitive vascular network [45]. Vasculogenesis and angiogenesis are involved in the development of the functional vascular system in the embryo and the formation of blood vessels in the postnatal period. Both vasculogenesis and angiogenesis are under the regulation of several growth factors, which include vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), platelet-derived growth factor (PDGF), and transforming growth factor β1 (TGF-β1), among others [45]. Interestingly, different research groups have found that Hox genes regulate the expression of these growth factors and, in turn, endothelial cell differentiation. In the next section, we will describe supporting evidence about the role of Hox genes in endothelial differentiation, vasculogenesis, and angiogenesis (**Figure 2**).
