Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Hidenobu Miyazawa, Yoshifumi Yamaguchi, Yuki Sugiura, Kurara Honda, Koki Kondo, Fumio Matsuda, Takehiro Yamamoto, Makoto Suematsu, Masayuki Miura

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flowinto the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK- 1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of themetabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development.

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalDevelopment (Cambridge)
Volume144
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

    Fingerprint

Keywords

  • Chorioallantoic branching
  • Energy metabolism
  • Imaging mass spectrometry
  • Lin28a
  • Mouse
  • Phosphofructokinase-1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this