Blech-Hermoni Yotam, Sullivan Connor B, Jenkins Michael W, Wessely Oliver, Ladd Andrea N
Program in Cell Biology, Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Dev Dyn. 2016 Aug;245(8):854-73. doi: 10.1002/dvdy.24413. Epub 2016 May 31.
CUG-BP, Elav-like family member 1 (CELF1) is a multifunctional RNA binding protein found in a variety of adult and embryonic tissues. In the heart, CELF1 is found exclusively in the myocardium. However, the roles of CELF1 during cardiac development have not been completely elucidated.
Myofibrillar organization is disrupted and proliferation is reduced following knockdown of CELF1 in cultured chicken primary embryonic cardiomyocytes. In vivo knockdown of Celf1 in developing Xenopus laevis embryos resulted in myofibrillar disorganization and a trend toward reduced proliferation in heart muscle, indicating conserved roles for CELF1 orthologs in embryonic cardiomyocytes. Loss of Celf1 also resulted in morphogenetic abnormalities in the developing heart and gut. Using optical coherence tomography, we showed that cardiac contraction was impaired following depletion of Celf1, while heart rhythm remained unperturbed. In contrast to cardiac muscle, loss of Celf1 did not disrupt myofibril organization in skeletal muscle cells, although it did lead to fragmentation of skeletal muscle bundles.
CELF1 is required for normal myofibril organization, proliferation, morphogenesis, and contractile performance in the developing myocardium. Developmental Dynamics 245:854-873, 2016. © 2016 Wiley Periodicals, Inc.
CUG-BP、Elav样家族成员1(CELF1)是一种多功能RNA结合蛋白,存在于多种成年和胚胎组织中。在心脏中,CELF1仅存在于心肌中。然而,CELF1在心脏发育过程中的作用尚未完全阐明。
在培养的鸡原代胚胎心肌细胞中敲低CELF1后,肌原纤维组织被破坏,增殖减少。在发育中的非洲爪蟾胚胎中体内敲低Celf1导致肌原纤维紊乱,心肌增殖有减少趋势,表明CELF1直系同源物在胚胎心肌细胞中具有保守作用。Celf1的缺失还导致发育中心脏和肠道的形态发生异常。使用光学相干断层扫描,我们发现敲低Celf1后心脏收缩受损,而心律保持不受干扰。与心肌不同,Celf1的缺失并未破坏骨骼肌细胞中的肌原纤维组织,尽管它确实导致了骨骼肌束的碎片化。
CELF1是发育中心肌正常肌原纤维组织、增殖、形态发生和收缩性能所必需的。《发育动力学》245:854 - 873,2016年。©2016威利期刊公司。