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
  • Animals
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/physiology
  • Embryonic Development/drug effects
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Hair Cells, Auditory/physiology
  • Lactic Acid/metabolism*
  • Lactic Acid/pharmacology
  • Mitogen-Activated Protein Kinases/metabolism*
  • Neurogenesis/drug effects*
  • Neurons/physiology
  • Phosphoglycerate Kinase/genetics
  • Receptors, Fibroblast Growth Factor
  • Reverse Genetics
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
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
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes