Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway: highlights from animal studies

Shahram Eisa-Beygi; Marc Ekker; Thomas W Moon; R Loch Macdonald; Xiao-Yan Wen

doi:10.1016/j.reprotox.2014.04.001

Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway: highlights from animal studies

Reprod Toxicol. 2014 Jul:46:115-20. doi: 10.1016/j.reprotox.2014.04.001. Epub 2014 Apr 13.

Authors

Shahram Eisa-Beygi¹, Marc Ekker², Thomas W Moon², R Loch Macdonald³, Xiao-Yan Wen⁴

Affiliations

¹ 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.
² Department of Biology, Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, ON, Canada.
³ 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.
⁴ 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.

PMID: 24732207
DOI: 10.1016/j.reprotox.2014.04.001

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.

Keywords: Cholesterol; Development; HMGCR; Prenylation; Statins; Teratogenesis; Toxicity.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Growth / physiology*
Hydroxymethylglutaryl CoA Reductases / genetics
Hydroxymethylglutaryl CoA Reductases / physiology*
Morphogenesis / genetics
Neovascularization, Physiologic / genetics
Neovascularization, Physiologic / physiology
Protein Prenylation / genetics
Protein Prenylation / physiology
Signal Transduction / physiology

Substances

Hydroxymethylglutaryl CoA Reductases