TM4SF1 is essential for embryonic blood vessel development

Transmembrane-4 L-six family member-1 (TM4SF1) is a small cell surface glycoprotein that is highly and selectively expressed on endothelial cells and mesenchymal stem cells. TM4SF1 regulates cellular functions by forming protein complexes called TMED (TM4SF1-enriched microdomains) that internalize via microtubules from the cell surface and transport recruited proteins to intracellular locations including the nucleus. Through a genetically manipulated mouse model, we demonstrate here that Tm4sf1 is essential for blood vessel development. Tm4sf1 null embryos fail to develop blood vessels and experience lethality at E9.5. Tm4SF1 heterozygous embryos are smaller in body size during early embryonic development, and almost half die in utero due to intracranial hemorrhage in the intraventricular and subarachnoid space which becomes apparent by E17.5. Surviving Tm4SF1 heterozygotes do not display overt phenotypic differences relative to wild type littermates postnatally. These findings confirm that Tm4sf1 is essential for embryonic blood vessel development.