Masayuki Oginuma(1,2), Yukiko Harima(2), Oscar A. Tarazona(2), Margarete Diaz-Cuadros(2), Arthur Michaut(2), Tohru Ishitani(2,3), Fengzhu Xiong(2), Olivier Pourquié (2) (1) Laboratory of Integrated Signaling Systems, Department of Molecular Medicine, Institute for Molecular & Cellular Regulation, Gunma University (2) Department of Genetics, Harvard Medical School (3) Department of Homeostatic Regulation, Division of Cellular and Molecular Biology, Research Institute for Microbial Diseases, Osaka University
Energy metabolism is a fundamental process of living systems, and well-studied in many biological processes. However, little is known about the role of energy metabolism during vertebrate embryogenesis. Previously we have found that vertebrate embryos show a glycolytic gradient in the posterior region of embryos (called as the tail bud), and glycolysis controls posterior patterning of embryos by regulating Wnt/β-catenin signaling (Oginuma et al., Developmental cell, 2017). However how glycolysis regulates WNT signaling is currently unknown. In this study, we found intracellular pH has a central role during this process. We found that the tail bud regions of chicken embryo and human tail bud-like cells differentiated in vitro from induced pluripotent stem cells show alkaline pH gradients under the glycolysis activities. This alkaline pH promotes β-catenin acetylation, that enhances WNT signaling activity. Similar alkaline pH by glycolysis is also observed in tumour cells. Our work supports the notion that some tumour cells reactivate a developmental metabolic programme.
Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Masayuki Oginuma, Yukiko Harima, Oscar A. Tarazona, Margarete Diaz-Cuadros, Arthur Michaut, Tohru Ishitani, Fengzhu Xiong & Olivier Pourquié. Nature.2020 Jun 24 doi: 10.1038/s41586-020-2428-0. Online ahead of print.