PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis

Caterina Pegoraro1, Ana Leonor Figueiredo1, Frédérique Maczkowiak1

  • 11] Université Paris Sud, Batiment 110, F-91 405 Orsay cedex, France [2] Institut Curie, Centre Universitaire, Batiment 110, F-91 405 Orsay cedex, France [3] CNRS UMR3347, Centre Universitaire, Batiment 110, F-91 405 Orsay cedex, France [4] INSERM U1021, Centre Universitaire, Batiment 110, F-91 405 Orsay cedex, France.

Nature Communications
|January 21, 2015
PubMed

Insights

Metabolism regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is crucial for early frog development, controlling cell fate specification through Akt signaling, not glycolysis.

Area of Science:

  • Developmental Biology
  • Cellular Metabolism
  • Molecular Signaling

Background:

  • The roles of metabolism regulators in early embryonic development are not fully understood.
  • Understanding how cellular processes influence developmental patterning is key to developmental biology.

Purpose of the Study:

  • To investigate the function of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) during early embryonic development.
  • To elucidate the mechanism by which PFKFB4 influences cell fate specification in frog embryos.

Main Methods:

  • Utilized frog embryos for in vivo studies.
  • Investigated the role of PFKFB4 in dorsal ectoderm patterning.
  • Examined the involvement of Akt signaling pathway.
  • Assessed the necessity of glycolysis for embryonic development.

Main Results:

  • PFKFB4 is essential for dorsal ectoderm progenitor specification, directing them towards neural and non-neural fates.
  • PFKFB4's function in cell fate determination is mediated by Akt signaling.
  • Restoration of Akt signaling rescues PFKFB4 loss-of-function phenotypes.
  • Glycolysis is not critical for frog development at this gastrulation stage.

Conclusions:

  • A PFKFB4-Akt signaling checkpoint regulates cell homeostasis and progenitor differentiation.
  • PFKFB4 possesses critical, non-glycolytic functions in early embryonic patterning.
  • This study reveals novel roles for metabolism regulators beyond their canonical metabolic functions.

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