Sakabe Masahide, Morioka Takashi, Kimura Hiroshi, Nakagawa Osamu
Laboratory for Cardiovascular System Research, Nara Medical University Advanced Medical Research Center, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
Second Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
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].
各种细胞信号通路在调节胚胎血管发育中发挥着重要作用。其中，Notch信号通路与动脉内皮分化和血管形态发生有关。缺乏Notch受体或其他信号成分的小鼠由于严重的血管异常在子宫内死亡。我们之前鉴定出毛相关转录（Hrt）因子家族，也称为Hey、Hesr、CHF、Herp和Gridlock，作为发育中的脉管系统中Notch信号通路的下游介质[1]。Hrt家族蛋白Hrt1/Hey1、Hrt2/Hey2和Hrt3/HeyL主要作为转录抑制因子，通过结合共有DNA元件或与其他DNA结合转录因子结合发挥作用。缺乏 的小鼠由于室间隔缺损和二尖瓣功能不全而在围产期死亡，并且在成年期心肌细胞特异性缺失 会导致心室中房特异性基因的异常表达和心脏功能障碍[2]。
