Both endothelial and erythroid cells are generated in the intermediate cell mass (ICM) during zebrafish embryogenesis, but the nature of the genes that contribute to the processes of erythrocyte maturation and blood vessel network formation is not fully understood. From our in situ-based screening, we have identified a novel factor, yap (Vascular Associated Protein) that is predominantly expressed in the ICM, and subsequently enriched in endothelial cells. yap expression in the ICM was drastically suppressed in the cloche mutant that has defects in both vasculogenesis and hematopoiesis, whereas yap expression was not affected in the vlad tepes/gata1 mutant. Knockdown of yap using anti-sense morpholinos (VAP-MO) not only resulted in decreased numbers of erythrocytes but also in the strong suppression of hemoglobin production. Further, we found that yap knockdown caused the disorganization of the intersegmental vessels (ISVs), which show irregular branching. We propose that yap plays an important role in the maturation of endothelial and erythroid cells in zebrafish. (C) 2012 Elsevier Inc. All rights reserved.