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Intracellular pH controls WNT downstream of glycolysis in amniote embryos.

Publication ,  Journal Article
Oginuma, M; Harima, Y; Tarazona, OA; Diaz-Cuadros, M; Michaut, A; Ishitani, T; Xiong, F; Pourquié, O
Published in: Nature
August 2020

Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic mesoderm, which control posterior elongation1, exhibit a high level of aerobic glycolysis that is reminiscent of the metabolic status of cancer cells experiencing the Warburg effect2,3. Glycolytic activity downstream of fibroblast growth factor controls WNT signalling in the tail bud3. In the neuromesodermal precursors of the tail bud4, WNT signalling promotes the mesodermal fate that is required for sustained axial elongation, at the expense of the neural fate3,5. How glycolysis regulates WNT signalling in the tail bud is currently unknown. Here we used chicken embryos and human tail bud-like cells differentiated in vitro from induced pluripotent stem cells to show that these cells exhibit an inverted pH gradient, with the extracellular pH lower than the intracellular pH, as observed in cancer cells6. Our data suggest that glycolysis increases extrusion of lactate coupled to protons via the monocarboxylate symporters. This contributes to elevating the intracellular pH in these cells, which creates a favourable chemical environment for non-enzymatic β-catenin acetylation downstream of WNT signalling. As acetylated β-catenin promotes mesodermal rather than neural fate7, this ultimately leads to activation of mesodermal transcriptional WNT targets and specification of the paraxial mesoderm in tail bud precursors. Our work supports the notion that some tumour cells reactivate a developmental metabolic programme.

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Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

August 2020

Volume

584

Issue

7819

Start / End Page

98 / 101

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • Mesoderm
  • Lactic Acid
  • Hydrogen-Ion Concentration
  • Humans
  • Glycolysis
  • General Science & Technology
  • Chick Embryo
  • Body Patterning
 

Citation

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Chicago
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Oginuma, M., Harima, Y., Tarazona, O. A., Diaz-Cuadros, M., Michaut, A., Ishitani, T., … Pourquié, O. (2020). Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Nature, 584(7819), 98–101. https://doi.org/10.1038/s41586-020-2428-0
Oginuma, Masayuki, Yukiko Harima, Oscar A. Tarazona, Margarete Diaz-Cuadros, Arthur Michaut, Tohru Ishitani, Fengzhu Xiong, and Olivier Pourquié. “Intracellular pH controls WNT downstream of glycolysis in amniote embryos.Nature 584, no. 7819 (August 2020): 98–101. https://doi.org/10.1038/s41586-020-2428-0.
Oginuma M, Harima Y, Tarazona OA, Diaz-Cuadros M, Michaut A, Ishitani T, et al. Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Nature. 2020 Aug;584(7819):98–101.
Oginuma, Masayuki, et al. “Intracellular pH controls WNT downstream of glycolysis in amniote embryos.Nature, vol. 584, no. 7819, Aug. 2020, pp. 98–101. Epmc, doi:10.1038/s41586-020-2428-0.
Oginuma M, Harima Y, Tarazona OA, Diaz-Cuadros M, Michaut A, Ishitani T, Xiong F, Pourquié O. Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Nature. 2020 Aug;584(7819):98–101.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

August 2020

Volume

584

Issue

7819

Start / End Page

98 / 101

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • Mesoderm
  • Lactic Acid
  • Hydrogen-Ion Concentration
  • Humans
  • Glycolysis
  • General Science & Technology
  • Chick Embryo
  • Body Patterning