Critical role for retinol in the generation/differentiation of angioblasts required for embryonic blood vessel formation.

Numerous studies demonstrate that vitamin A (retinol) deficiency causes abnormal cardiovascular morphogenesis. We evaluated the impact of retinol deficiency on the regulation of the numbers of endothelial cells and angioblasts (endothelial progenitors) produced during embryonic quail development. At the one-somite stage, there were no discernible differences in the mean number of endothelial cells or angioblasts in normal and retinol-deficient embryos. However, retinol-deficient embryos at the three-somite stage had an increase in the mean number of endothelial cells but no difference in the mean number of angioblasts. By contrast, retinol-deficient embryos at the five-somite stage have 61% of the normal number of endothelial cells and 12% of the normal number of angioblasts. Similarly, retinol-deficient embryos at the 10-somite stage had 71% and 60% of normal numbers of endothelial cells in capillary-like networks and the sinuses venosus, respectively. Furthermore, we show that retinol deficiency did not elicit a global reduction in mesodermal cell numbers but was specific to cells of the endothelial lineage. Taken together, our findings suggest that vascular abnormalities observed under conditions of retinol deficiency are due to reduction in the number of angioblasts and consequently an insufficiency in the number of endothelial cells required to build complex vascular networks.