PUBLICATION
The mevalonate pathway regulates primitive streak formation via protein farnesylation
- Authors
- Okamoto-Uchida, Y., Yu, R., Miyamura, N., Arima, N., Ishigami-Yuasa, M., Kagechika, H., Yoshida, S., Hosoya, T., Nawa, M., Kasama, T., Asaoka, Y., Alois, R.W., Elling, U., Penninger, J.M., Nishina, S., Azuma, N., Nishina, H.
- ID
- ZDB-PUB-180531-16
- Date
- 2016
- Source
- Scientific Reports 6: 37697 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Neurogenesis
- Oligonucleotide Array Sequence Analysis
- Organogenesis
- Cell Differentiation
- Zebrafish
- Mevalonic Acid/metabolism*
- Primitive Streak/embryology*
- Primitive Streak/metabolism*
- Down-Regulation/genetics
- Gene Expression Regulation, Developmental
- Protein Prenylation*
- Embryoid Bodies
- Metabolic Networks and Pathways*
- Metabolome
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Animals
- Mice, Inbred ICR
- Metabolomics
- PubMed
- 27883036 Full text @ Sci. Rep.
Citation
Okamoto-Uchida, Y., Yu, R., Miyamura, N., Arima, N., Ishigami-Yuasa, M., Kagechika, H., Yoshida, S., Hosoya, T., Nawa, M., Kasama, T., Asaoka, Y., Alois, R.W., Elling, U., Penninger, J.M., Nishina, S., Azuma, N., Nishina, H. (2016) The mevalonate pathway regulates primitive streak formation via protein farnesylation. Scientific Reports. 6:37697.
Abstract
The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis. A tagging-via-substrate approach revealed that nuclear lamin B1 and small G proteins were farnesylated in embryoid bodies and important for primitive streak gene expression. In conclusion, protein farnesylation driven by the mevalonate pathway is a metabolic cue essential for primitive streak formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping