Molecular and developmental biology of the hemangioblast - PubMed (original) (raw)

Review

Molecular and developmental biology of the hemangioblast

Jing-Wei Xiong. Dev Dyn. 2008 May.

Abstract

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.

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Figures

Figure 1

Figure 1. Molecular signaling that regulates hemangioblast, endothelial and hematopoietic lineage development in the gastrula and during somitogenesis of zebrafish, chick and mouse embryos

This simplified cartoon shows putative signaling pathways controlling hemangioblast development in zebrafish, chick and mouse embryos. During gastrulation, the ventral mesoderm in zebrafish and the posterior primitive streak in chick and mice are induced by morphogens such as BMPs and FGFs. These mesodermal cells will then contribute to the formation of the hemangioblast as well as endothelial and hematopoietic lineages that are independent of the hemangioblast in the anterior and posterior lateral plate mesoderm (LPM) in zebrafish, and the extraembryonic yolk sac blood islands in chick and mice. cloche, bmp4, vegf, lycat, and hhex are important for these lineage development in zebrafish. It is hypothesized that these signals are from the extraembryonic yolk sac syncytial layer in zebrafish. In chick and/or mouse embryos and/or embryoid bodies, Bmp4, Vegf, Ihh, Shh, RA, Lycat, Hhex, and Mixl1 are shown to be expressed in the primitive visceral endoderm and/or mesoderm and be essential for the generation of these lineages in the extraembryonic blood islands. The hemangioblast (HM) will give rise to endothelial cells (ECs), induced by Etsrp and Hhex, and blood cells (BL), induced by ZBP-89, Scl and Lmo2, in the anterior and posterior LPM in zebrafish and the yolk sac blood islands in chick and mice. In zebrafish, chick and mouse embryos at late somite stages, Runx1 and C-Myb are expressed in the hemogenic endothelial cells (also called definitive hemangioblasts) of the ventral and para aorta, and are required for the formation of hematopoietic cells from the hemogenic endothelial cells.

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