Understanding early stages of hematopoietic stem cell maturation during mouse embryogenesis

Abstract

embryonic development. Here we show that the Zebrafish Stab2 homolog is specifically expressed in vascular endothelial cells during early embryonic development. Its expression is first restricted to the arterial progenitors, while by 24 hpf its expression is downregulated in the arterial and upregulated in the venous vasculature. Stab2 morpholino knockdown embryos (morphants) display an absence of intersegmental vessels and gaps in axial vessels. In addition, Stab2 morphants show defects in arterial–venous differentiation including the expansion of venous markers into the dorsal aorta, as well as the expansion of arterial markers into the cardinal vein. This suggests that Stab2 function is required tomaintain arterial–venous identity. Simultaneous knockdown of Stabilin2 and has2, a hyaluronic acid (HA) synthetase, results in a synergistic effect; arguing that HA and Stab2 interact during vasculature formation. ERK phosphorylation has been previously associated with arterial–venous patterning. The pattern of ERK phosphorylation is disrupted in Stab2 morphants, and ectopic ERK phosphorylation in venous progenitors is observed. In addition, VEGF signaling is involved in maintaining arterial–venous pattern of Stab2 expression while Notch signaling appears to be dispensable in this process. These results argue that HA–Stab2 signaling plays an important role in establishing arterial– venous identity by regulating ERK phosphorylation pattern.