In mouse mid-gestational embryos,definitive hematopoietic stem progenitor cells are derived directly from a very small proportion of the arterial endothelium.However,the physiological mechanisms restraining excessive endothelial-hematopoietic transition remain elusive.We show here that genetic deletion of Smad4 from the endothelium stage (using Tie2-Cre),but not from embryonic hematopoietic cells (using Vav-Cre),leads to a strikingly augmented emergence of intra-arterial hematopoietic clusters and an enhanced in vitro generation of hematopoietic progenitors,with no increase in the proliferation and survival ofhematopoietic cluster cells.