ZFIN ID: ZDB-PUB-200428-2
The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle
Kantarci, H., Gou, Y., Riley, B.B.
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
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.