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The mevalonate pathway regulates primitive streak formation via protein farnesylation

Yoshimi Okamoto-Uchida1,2, Ruoxing Yu1, Norio Miyamura1

  • 1Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.

Scientific Reports
|November 25, 2016
PubMed

Insights

Protein farnesylation, regulated by the mevalonate pathway, is crucial for primitive streak formation in early embryos. This metabolic process is essential for mesoderm and endoderm development and cell differentiation.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Metabolic Regulation

Background:

  • The primitive streak is vital for embryonic development, establishing mesoderm and endoderm.
  • Metabolic regulation of primitive streak formation is not well understood.

Purpose of the Study:

  • To identify metabolic factors regulating primitive streak formation.
  • To elucidate the role of the mevalonate pathway in early embryonic development.

Main Methods:

  • Used a mouse embryonic stem cell differentiation system.
  • Employed a drug library, metabolomics, and pharmacologic approaches.
  • Utilized a tagging-via-substrate method to identify farnesylated proteins.

Main Results:

  • Statins, inhibiting the mevalonate pathway, suppressed primitive streak formation.
  • Protein farnesylation, not cholesterol synthesis, is required for primitive streak formation.
  • Nuclear lamin B1 and small G proteins were identified as farnesylated targets essential for gene expression.

Conclusions:

  • The mevalonate pathway and subsequent protein farnesylation are critical metabolic cues for primitive streak formation.
  • This study reveals a novel link between metabolic pathways and early embryonic patterning.

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