% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Miyazawa:182896,
      author       = {H. Miyazawa and M. T. Snaebjörnsson$^*$ and N. Prior and
                      E. Kafkia and H. M. Hammarén and N. Tsuchida-Straeten and
                      K. R. Patil and M. Beck and A. Aulehla},
      title        = {{G}lycolytic flux-signaling controls mouse embryo mesoderm
                      development.},
      journal      = {eLife},
      volume       = {11},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DKFZ-2022-02999},
      pages        = {e83299},
      year         = {2022},
      note         = {#EA:A410#},
      abstract     = {How cellular metabolic state impacts cellular programs is a
                      fundamental, unresolved question. Here we investigated how
                      glycolytic flux impacts embryonic development, using
                      presomitic mesoderm (PSM) patterning as the experimental
                      model. First, we identified fructose 1,6-bisphosphate (FBP)
                      as an in vivo sentinel metabolite that mirrors glycolytic
                      flux within PSM cells of post-implantation mouse embryos. We
                      found that medium-supplementation with FBP, but not with
                      other glycolytic metabolites, such as fructose 6-phosphate
                      and 3-phosphoglycerate, impaired mesoderm segmentation. To
                      genetically manipulate glycolytic flux and FBP levels, we
                      generated a mouse model enabling the conditional
                      overexpression of dominant active, cytoplasmic PFKFB3
                      (cytoPFKFB3). Overexpression of cytoPFKFB3 indeed led to
                      increased glycolytic flux/FBP levels and caused an
                      impairment of mesoderm segmentation, paralleled by the
                      downregulation of Wnt-signaling, reminiscent of the effects
                      seen upon FBP-supplementation. To probe for mechanisms
                      underlying glycolytic flux-signaling, we performed
                      subcellular proteome analysis and revealed that cytoPFKFB3
                      overexpression altered subcellular localization of certain
                      proteins, including glycolytic enzymes, in PSM cells.
                      Specifically, we revealed that FBP supplementation caused
                      depletion of Pfkl and Aldoa from the nuclear-soluble
                      fraction. Combined, we propose that FBP functions as a
                      flux-signaling metabolite connecting glycolysis and PSM
                      patterning, potentially through modulating subcellular
                      protein localization.},
      keywords     = {developmental biology (Other) / mouse (Other)},
      cin          = {A410},
      ddc          = {600},
      cid          = {I:(DE-He78)A410-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36469462},
      doi          = {10.7554/eLife.83299},
      url          = {https://inrepo02.dkfz.de/record/182896},
}