title: Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching.
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.
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hidenobu
authors.identifier: 0000-0001-6164-5134
authors.initials: H
authors.lastname: Miyazawa
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan bunbun@mol.f.u-tokyo.ac.jp miura@mol.f.u-tokyo.ac.jp.|Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Yoshifumi
authors.identifier: 0000-0001-7340-4557
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan.|Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kurara
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Fumio
authors.identifier: 0000-0003-1091-778X
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takehiro
authors.identifier: 0000-0003-4974-9859
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.identifier: 0000-0002-7165-6336
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan bunbun@mol.f.u-tokyo.ac.jp miura@mol.f.u-tokyo.ac.jp.|Agency for Medical Research and Development-Core Research for Evolutional Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-1004, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
mesh_terms: D000818:Animals; D049033:Chorioallantoic Membrane / Q000196:embryology* / Q000378:metabolism*; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D008431:Maternal-Fetal Exchange / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D010732:Phosphofructokinase-1 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology
chemical_list: C488352:Lin-28 protein, mouse; D016601:RNA-Binding Proteins; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose
keywords: Chorioallantoic branching; Energy metabolism; Imaging mass spectrometry; Lin28a; Mouse; Phosphofructokinase-1