Molecular and developmental biology of the hemangioblast.

The hemangioblast hypothesis was proposed a century ago. The existence of hemangioblasts is now demonstrated in mouse and human embryonic stem cell (ESC)-derived embryoid bodies (EBs), in the mouse and zebrafish gastrula, and in adults. The hemangioblast is believed to derive from mesodermal cells, and is enriched in the Bry+Flk1+ and Flk1+Scl+ cell populations in EBs and in the posterior primitive streak of the mouse gastrula and in the ventral mesoderm of the zebrafish gastrula. However, recent studies suggest that the hemangioblast does not give rise to all endothelial and hematopoietic lineages in mouse and zebrafish embryos. Although several signaling pathways are known to involve the generation of hemangioblasts, it remains largely unknown how the hemangioblast is formed and what are the master genes controlling hemangioblast development. This review will summarize our current knowledge, challenges, and future directions on molecular and developmental aspects of the hemangioblast.