However, because Spry1, Spry2, and Spry4 are all expressed in Flk1 + mesodermal cells and expressed in VEC + cells, other Spry proteins may compensate for the NVP-BKM120 effect of changes in Spry1 expression on endothelial formation. Although endothelial cell development in Spry1;Tie2-Cre WZ8040 embryos is normal, and the number of VEC + cells in whole mount stained E9.5 yolk sacs of Spry1;Tie2-Cre appears similar to or greater than wild type controls, there is a failure of vascular remodeling in Spry1;Tie2 yolk sacs as evidenced by a lack of larger vessels. Vascular integrity also appears compromised in Spry1;Tie2-Cre yolk sacs because autofluorescent blood cells were not contained with in vessels the way they are in wild type control yolk sacs. Hematopoietic cells derive from hemogenic endothelial cells, which express Tie2, Flk1, VEC, and endoglin all markers of endothelial cells and expression of these endothelial marker genes are decreased after hematopoietic commitment and differentiation. By FACS analysis we also showed that newly emerging hematopoietic cells co-express Tie2 and Flk1 both in wild type and Spry1;Tie2-Cre embryos and yolk sacs. It is reasonable to expect that in wild type embryos mature blood cells do not express endothelial markers, however in Spry1;Tie2-Cre mice, over-expression of Spry1 may delay the downregulation of endothelial markers in committed hematopoietic cells even after further differentiation. Further study is necessary to address this phenomenon. Although endothelial cell development seems unaffected by over-expression of Spry1, we observed vascular defects including discontinuous endocardium and failure of vascular invasion of the neural tube in Spry1;Tie2-Cre transgenic embryos suggesting Spry1- expressing endothelial cells have impaired functions in vivo. Because Sprys inhibit branching morphogenesis in Drosophila and mice, and vascular network formation of HUVEC on Matrigel, it is possible that the vascular defects we observed in Spry1;Tie2-Cre yolk sacs and embryos is due to Spry1 over expression directly, or alternatively this defect may be indirectly the result of reduced hematopoietic cells and blood flow. Other studies have shown that defects in hematopoiesis contribute to vascular remodeling defects through changes in hemodynamic forces and cytokine production. To gain more insight into the vascular defects associate with Spry expression, additional studies using endothelial cell specific Cre-mediated gain- and lossof- function of Spry1 alone or in combination with other Spry family members will be necessary to address this issue. Roundworm and flatworm infections, known as helminth infections, are an enormous problem worldwide, especially in developing countries.