A compendium of expression patterns of cholesterol biosynthetic enzymes in the mouse embryo

Melda Şişecioğlu, Harun Budak, Lars Geffers, Murat Çankaya, Mehmet Çiftci, Christina Thaller, Gregor Eichele, Ömer İrfan Küfrevioğlu, Hasan Özdemir

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cholesterol and its biosynthetic pathway intermediates and derivatives are required for many developmental processes including membrane biogenesis, transmembrane receptor signaling, steroid biogenesis, nuclear receptor activation, and posttranslational modification of hedgehog (Hh) proteins. To perform such multifaceted tasks depends on stringent regulation of expression of cholesterol biosynthetic enzymes (CBEs). We established for a whole organism, for the first time, the 3D expression pattern of all genes required for cholesterol biosynthesis (CBS), starting from acetyl-CoA and ending with cholesterol. This data was produced by high-throughput in situ hybridization on serial sections through the mouse fetus. The textually annotated image data were seamlessly integrated into the METscout and GenePaint public databases. This novel information helps in the understanding of why CBEs are expressed at particular locations within the fetus. For example, strong CBE expression is detected at sites of cell proliferation and also where cell growth increases membrane surface, such as in neurons sprouting axons and forming synapses. The CBE data also sheds light on the spatial relationship of cells and tissue that express sonic Hh (Shh) and produce cholesterol, respectively. We discovered that not all cells expressing Shh are capable of CBS. This finding suggests novel ways by which cholesterylation of Shh is regulated.

Original languageEnglish
Pages (from-to)1551-9
Number of pages9
JournalJournal of Lipid Research
Volume56
Issue number8
DOIs
Publication statusPublished - Aug 2015
Externally publishedYes

Keywords

  • Animals
  • Cholesterol/biosynthesis
  • Embryo, Mammalian/enzymology
  • Energy Metabolism
  • Gene Expression Regulation, Developmental
  • Mice

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