![]() The authors executed several experiments aimed at disrupting growth factor signaling or the erythroid specification program in the VBI and then assessed how these manipulations affected the development of blood vs endothelial lineages within the VBI. Myers and Krieg, however, performed a further series of experiments, which were especially revealing and may explain what the hemangioblast represents in developmental terms. Thus, they concluded that the VBI in early frog embryos does not contain bipotential precursor cells that give rise to both blood and endothelial lineages, and thus, that the this region does not contain what has been classically defined as hemangioblasts in vivo. The results from these experiments showed that the VBI will normally only give rise to blood lineages and not endothelial lineages in vivo. Finally Myers and Krieg performed a further set of fate mapping studies, using homotypic transplants, to ask whether the normal fate of the VBI was to give rise to both blood and endothelial lineages, or only blood, as suggested by their specification mapping studies. ![]() These results suggested that the VBI is specified only to give rise to blood cells. They isolated and cultured the VBI as explants, to ask whether this tissue could form both lineages when cultured in isolation? The answer was that the isolated VBI explants could only give rise to blood but not endothelial lineages. Thus, Myers and Krieg performed a series of classic specification assays. However, these findings did not exclude the possibility that some endothelial lineages may still arise from the VBI, albeit in smaller numbers. This finding suggested that the VBI is not a major source of endothelial cells in the early embryo. First, they removed the VBI from early embryos and asked whether embryos lacking a VBI would go on to express both primitive blood and endothelial markers at later stages? The answer was that removal of the VBI resulted in a clear loss of primitive blood lineages, but the endothelial lineages remained intact. To answer this question, they performed a series of experiments aimed at finally putting this issue to rest. ![]() However the question had remained unresolved as to whether these cells represented bona fide hemangioblasts in vivo. Previously, it had already been shown that cells in the VBI of frog embryos express both hematopoietic and endothelial markers, consistent with the putative hemangioblasts. The VBI in amphibian embryos is analogous to the yolk sac in chick and mouse embryos, the site where hemangioblasts were first postulated to exist, and thus it provides a convenient complementary model system to tackle this question. In this paper, Myers and Krieg weigh into this controversy by performing a series of elegant experiments asking whether the ventral blood island (VBI) in the early frog embryo has cells consistent with the hypothetical hemangioblast.
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