title: FGF signalling specifies haematopoietic stem cells through its regulation of somitic Notch signalling.
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.
authors.affiliation: Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Yoonsung
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Manegold
authors.affiliation: Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Kim
authors.affiliation: Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.affiliation: 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.
authors.forename: David L
authors.initials: DL
authors.lastname: Stachura
authors.affiliation: 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.
authors.forename: Wilson K
authors.initials: WK
authors.lastname: Clements
authors.affiliation: Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: David
authors.initials: D
authors.lastname: Traver
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051881:Receptor, Notch1; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C064045:delta protein; C468126:dld protein, zebrafish; C437805:notch1a protein, zebrafish; C559646:wnt16 protein, zebrafish; D051499:Receptor, Fibroblast Growth Factor, Type 4; C496375:fgfr4 protein, zebrafish