PUBLICATION

EGFR is required for Wnt9a-Fzd9b signalling specificity in haematopoietic stem cells

Authors
Grainger, S., Nguyen, N., Richter, J., Setayesh, J., Lonquich, B., Oon, C.H., Wozniak, J.M., Barahona, R., Kamei, C.N., Houston, J., Carrillo-Terrazas, M., Drummond, I.A., Gonzalez, D., Willert, K., Traver, D.
ID
ZDB-PUB-190522-1
Date
2019
Source
Nature cell biology   21(6): 721-730 (Journal)
Registered Authors
Drummond, Iain, Grainger, Stephanie, Richter, Jana, Traver, David
Keywords
none
MeSH Terms
  • Animals
  • ErbB Receptors/genetics
  • Hematopoietic Stem Cells/cytology*
  • Humans
  • Phosphorylation
  • Receptors, Neurotransmitter/genetics*
  • Wnt Proteins/genetics*
  • Wnt Signaling Pathway
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • beta Catenin/genetics
PubMed
31110287 Full text @ Nat. Cell Biol.
Abstract
Wnt signalling drives many processes in development, homeostasis and disease; however, the role and mechanism of individual ligand-receptor (Wnt-Frizzled (Fzd)) interactions in specific biological processes remain poorly understood. Wnt9a is specifically required for the amplification of blood progenitor cells during development. Using genetic studies in zebrafish and human embryonic stem cells, paired with in vitro cell biology and biochemistry, we determined that Wnt9a signals specifically through Fzd9b to elicit β-catenin-dependent Wnt signalling that regulates haematopoietic stem and progenitor cell emergence. We demonstrate that the epidermal growth factor receptor (EGFR) is required as a cofactor for Wnt9a-Fzd9b signalling. EGFR-mediated phosphorylation of one tyrosine residue on the Fzd9b intracellular tail in response to Wnt9a promotes internalization of the Wnt9a-Fzd9b-LRP signalosome and subsequent signal transduction. These findings provide mechanistic insights for specific Wnt-Fzd signals, which will be crucial for specific therapeutic targeting and regenerative medicine.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes