Roles of Endothelial Hrt Genes for Vascular Development

Various cellular signaling pathways play essential roles in regulating embryonic vascular development. Among them, Notch signaling is implicated in arterial endothelium differentiation and vascular morphogenesis. Mice that lack Notch receptors or other signaling components die in utero due to severe vascular abnormalities. We previously identified the Hairy-related transcription (Hrt) factor family, also called Hey, Hesr, CHF, Herp, and Gridlock, as downstream mediators of Notch signaling in the developing vasculature [1]. The Hrt family proteins, Hrt1/Hey1, Hrt2/Hey2, and Hrt3/HeyL, mainly act as transcriptional repressors, by binding to consensus DNA elements or by associating with other DNA-binding transcription factors. The mice deficient for showed perinatal lethality due to ventricular septal defects and mitral valve insufficiency, and cardiomyocyte-specific deletion of caused abnormal expression of atrial-specific genes in the ventricle and cardiac dysfunction in adulthood [2].