PUBLICATION

The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle

Authors
Kantarci, H., Gou, Y., Riley, B.B.
ID
ZDB-PUB-200428-2
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Riley, Bruce
Keywords
developmental biology, zebrafish
MeSH Terms
  • Signal Transduction
  • Hair Cells, Auditory/physiology
  • Mitogen-Activated Protein Kinases/metabolism*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Fibroblast Growth Factors/metabolism*
  • Phosphoglycerate Kinase/genetics
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Receptors, Fibroblast Growth Factor
  • Embryonic Development/drug effects
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/physiology
  • Lactic Acid/metabolism*
  • Lactic Acid/pharmacology
  • Neurons/physiology
  • Neurogenesis/drug effects*
  • Animals
  • Reverse Genetics
(all 21)
PubMed
32338604 Full text @ Elife
Abstract
Recent studies indicate that many developing tissues modify glycolysis to favor lactate synthesis, but how this promotes development is unclear. Using forward and reverse genetics in zebrafish, we show that disrupting the glycolytic gene phosphoglycerate kinase-1 (pgk1) impairs Fgf-dependent development of hair cells and neurons in the otic vesicle and other neurons in the CNS/PNS. Fgf-MAPK signaling underperforms in pgk1-/- mutants even when Fgf is transiently overexpressed. Wild-type embryos treated with drugs that block synthesis or secretion of lactate mimic the pgk1-/- phenotype, whereas pgk1-/- mutants are rescued by treatment with exogenous lactate. Lactate treatment of wild-type embryos elevates expression of Etv5b/Erm even when Fgf signaling is blocked. However, lactate's ability to stimulate neurogenesis is reversed by blocking MAPK. Thus, lactate raises basal levels of MAPK and Etv5b (a critical effector of the Fgf pathway), rendering cells more responsive to dynamic changes in Fgf signaling required by many developing tissues.
Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ABchemical treatment by environment: 2-deoxy-D-glucosePrim-5
ABchemical treatment by environment: alpha-cyano-4-hydroxycinnamic acid14-19 somites
ABchemical treatment by environment: alpha-cyano-4-hydroxycinnamic acidPrim-5
ABchemical treatment by environment: alpha-cyano-4-hydroxycinnamic acid, chemical treatment by environment: lactate14-19 somites
ABchemical treatment by environment: ATP, chemical treatment by environment: enzyme inhibitorPrim-5
ABchemical treatment by environment: enzyme inhibitor14-19 somites
ABchemical treatment by environment: enzyme inhibitorPrim-5
ABchemical treatment by environment: enzyme inhibitor, chemical treatment by environment: lactate14-19 somites
ABchemical treatment by environment: enzyme inhibitor, chemical treatment by environment: lactatePrim-5
ABchemical treatment by environment: lactate14-19 somites
1 - 10 of 123
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Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Fish
Fish
AB
pd1Tg
pgk1x40/x40
pgk1x40/x40; s356tTg
pgk1x40/x40; x65Tg; zc7Tg
pgk1x40/x40; zc7Tg
pgk1x40/x40; zc7Tg + MO1-plg + MO4-tp53
pgk1x55/x55
pgk1x55/x55; x17Tg
pgk1x55/x55; x66Tg; zc7Tg
1 - 10 of 24
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Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
GFPEFGGFP
1 - 2 of 2
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Mapping
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Citation
Kantarci, H., Gou, Y., Riley, B.B. (2020) The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle. eLIFE. 9:.