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Nat Commun. 2014 Nov 27;5:5583. doi: 10.1038/ncomms6583.

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

Author information

1
Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
2
1] Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA [2] Department of Biological Sciences, California State University, Chico, California 95929, USA.
3
1] Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA [2] Department of Hematology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

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.

PMID:
25428693
PMCID:
PMC4271318
DOI:
10.1038/ncomms6583
[Indexed for MEDLINE]
Free PMC Article

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