title: Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway: highlights from animal studies.
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.
authors.affiliation: 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. Electronic address: shahram@alumni.uottawa.ca.
authors.forename: Shahram
authors.initials: S
authors.lastname: Eisa-Beygi
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, ON, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ekker
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, ON, Canada.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
authors.affiliation: 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; Division of Neurosurgery, St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
authors.affiliation: 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.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wen
mesh_terms: D000818:Animals; D006128:Growth / Q000502:physiology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D017368:Protein Prenylation / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006903:Hydroxymethylglutaryl CoA Reductases
keywords: Cholesterol; Development; HMGCR; Prenylation; Statins; Teratogenesis; Toxicity