PUBLICATION

FGF signalling specifies haematopoietic stem cells through its regulation of somitic Notch signalling

Authors
Lee, Y., Manegold, J.E., Kim, A.D., Pouget, C., Stachura, D.L., Clements, W.K., Traver, D.
ID
ZDB-PUB-170214-264
Date
2014
Source
Nature communications   5: 5583 (Journal)
Registered Authors
Clements, Wilson, Lee, Yoonsung, Traver, David
Keywords
Cell signalling, Haematopoietic stem cells
MeSH Terms
  • Animals
  • Cell Differentiation
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Receptor, Fibroblast Growth Factor, Type 4/genetics
  • Receptor, Fibroblast Growth Factor, Type 4/metabolism*
  • Receptor, Notch1/genetics
  • Receptor, Notch1/metabolism
  • Signal Transduction
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
25428693 Full text @ Nat. Commun.
Abstract
Haematopoietic stem cells (HSCs) derive from haemogenic endothelial cells of the primitive dorsal aorta (DA) during vertebrate embryogenesis. The molecular mechanisms governing this unique endothelial to haematopoietic transition remain unclear. Here, we demonstrate a novel requirement for fibroblast growth factor (FGF) signalling in HSC emergence. This requirement is non-cell-autonomous, and acts within the somite to bridge the Wnt and Notch signalling pathways. We previously demonstrated that Wnt16 regulates the somitic expression of two Notch ligands, deltaC (dlc) and deltaD (dld), whose combined function is required for HSC fate. How Wnt16 connects to Notch function has remained an open question. Our current studies demonstrate that FGF signalling, via FGF receptor 4 (Fgfr4), mediates a signal-transduction pathway between Wnt16 and Dlc, but not Dld, to regulate HSC specification. Our findings demonstrate that FGF signalling acts as a key molecular relay within the developmental HSC niche to instruct HSC fate.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping