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Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway: highlights from
Shahram Eisa-Beygi1, Marc Ekker2, Thomas W Moon2
1Department 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.
Abstract:
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.
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