Eisa-Beygi Shahram, Ekker Marc, Moon Thomas W, Macdonald R Loch, Wen Xiao-Yan
Department of Biology, Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, ON, Canada; Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science & Department of Medicine, University of Toronto, ON, Canada.
Department of Biology, Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, ON, Canada.
Reprod Toxicol. 2014 Jul;46:115-20. doi: 10.1016/j.reprotox.2014.04.001. Epub 2014 Apr 13.
The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in the biosynthesis of cholesterol and isoprenoids, which are substrates required for post-translational modification of signalling proteins that can potentially regulate various aspects of embryonic development. The HMGCR transcripts are detectable during early embryogenesis in both invertebrates and vertebrates, which suggests a conserved developmental requirement for mevalonate derivatives. Consistently, recent animal and in vitro studies have yielded valuable insights into potential morphogenic parameters that are modulated by HMGCR activity. These developmental end-points include brain and craniofacial morphogenesis, PGC migration and survival, myocardial epithelial migration and fusion, EC migration and survival, and vascular stabilization. By providing a synthesis of these studies, we hope that this review will highlight the need to comprehensively examine the entire suite of developmental processes regulated by HMGCR.
3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）是胆固醇和类异戊二烯生物合成中的限速酶，而胆固醇和类异戊二烯是信号蛋白翻译后修饰所需的底物，这些信号蛋白可能调节胚胎发育的各个方面。在无脊椎动物和脊椎动物的早期胚胎发育过程中均可检测到HMGCR转录本，这表明甲羟戊酸衍生物在发育过程中具有保守的需求。同样，最近的动物和体外研究对受HMGCR活性调节的潜在形态发生参数提供了有价值的见解。这些发育终点包括脑和颅面形态发生、生殖细胞迁移和存活、心肌上皮迁移和融合、内皮细胞迁移和存活以及血管稳定。通过综合这些研究，我们希望本综述将突出全面研究由HMGCR调节的整个发育过程的必要性。
