Through genetic manipulation approaches, we demonstrate here that Tm4sf1-null mice experience embryonic lethality by E9.5 due to a failure to form blood vessels, and that the suboptimal level of TM4SF1 in Tm4sf1-heterozygotes causes a smaller body size during early embryonic development with almost half of the embryos experiencing a lethal vascular defect in the head that led to intraventricular and subarachnoid hemorrhage. This evidence concerns the gene TM4SF1 and subarachnoid hemorrhage.