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.
Abstract:
How metabolism regulators play roles during early development remains elusive. Here we show that PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4), a glycolysis regulator, is critical for controlling dorsal ectoderm global patterning in gastrulating frog embryos via a non-glycolytic function. PFKFB4 is required for dorsal ectoderm progenitors to proceed towards more specified fates including neural and non-neural ectoderm, neural crest or placodes. This function is mediated by Akt signalling, a major pathway that integrates cell homeostasis and survival parameters. Restoring Akt signalling rescues the loss of PFKFB4 in vivo. In contrast, glycolysis is not essential for frog development at this stage. Our study reveals the existence of a PFKFB4-Akt checkpoint that links cell homeostasis to the ability of progenitor cells to undergo differentiation, and uncovers glycolysis-independent functions of PFKFB4.
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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