FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway

Claire Pouget, Tessa Peterkin, Filipa Costa Simões, Yoonsung Lee, David Traver () and Roger Patient ()
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Claire Pouget: Section of Cell and Developmental Biology, University of California, La Jolla
Tessa Peterkin: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford
Filipa Costa Simões: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford
Yoonsung Lee: Section of Cell and Developmental Biology, University of California, La Jolla
David Traver: Section of Cell and Developmental Biology, University of California, La Jolla
Roger Patient: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Haematopoietic stem cells (HSCs) are produced during embryogenesis from the floor of the dorsal aorta. The localization of HSCs is dependent on the presence of instructive signals on the ventral side of the vessel. The nature of the extrinsic molecular signals that control the aortic haematopoietic niche is currently poorly understood. Here we demonstrate a novel requirement for FGF signalling in the specification of aortic haemogenic endothelium. Our results demonstrate that FGF signalling normally acts to repress BMP activity in the subaortic mesenchyme through transcriptional inhibition of bmp4, as well as through activation of two BMP antagonists, noggin2 and gremlin1a. Taken together, these findings demonstrate a key role for FGF signalling in establishment of the developmental HSC niche via its regulation of BMP activity in the subaortic mesenchyme. These results should help inform strategies to recapitulate the development of HSCs in vitro from pluripotent precursors.

Date: 2014
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DOI: 10.1038/ncomms6588

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