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

Development. 2017 Jan 1;144(1):63-73. doi: 10.1242/dev.138545.

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 flow into 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 the metabolic 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.

Keywords: Chorioallantoic branching; Energy metabolism; Imaging mass spectrometry; Lin28a; Mouse; Phosphofructokinase-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chorioallantoic Membrane / embryology*
  • Chorioallantoic Membrane / metabolism*
  • Embryo, Mammalian
  • Embryonic Development / genetics
  • Energy Metabolism / genetics*
  • Female
  • Fructose-Bisphosphate Aldolase / genetics*
  • Fructose-Bisphosphate Aldolase / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Glucose / metabolism*
  • Glycolysis / genetics
  • Maternal-Fetal Exchange / genetics
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Phosphofructokinase-1 / genetics*
  • Phosphofructokinase-1 / metabolism
  • Pregnancy
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology

Substances

  • Lin-28 protein, mouse
  • RNA-Binding Proteins
  • Phosphofructokinase-1
  • Fructose-Bisphosphate Aldolase
  • Glucose