Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2

June Baik, Alessandro Magli, Naoyuki Tahara, Scott A. Swanson, Naoko Koyano-Nakagawa, Luciene Borges, Ron Stewart, Daniel J. Garry, Yasuhiko Kawakami, James A. Thomson and Rita C. R. Perlingeiro ()
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June Baik: Lillehei Heart Institute, University of Minnesota
Alessandro Magli: Lillehei Heart Institute, University of Minnesota
Naoyuki Tahara: Cell Biology, and Development, University of Minnesota
Scott A. Swanson: Regerative Biology, Morgridge Institute for Research
Naoko Koyano-Nakagawa: Lillehei Heart Institute, University of Minnesota
Luciene Borges: Lillehei Heart Institute, University of Minnesota
Ron Stewart: Regerative Biology, Morgridge Institute for Research
Daniel J. Garry: Lillehei Heart Institute, University of Minnesota
Yasuhiko Kawakami: Cell Biology, and Development, University of Minnesota
James A. Thomson: Regerative Biology, Morgridge Institute for Research
Rita C. R. Perlingeiro: Lillehei Heart Institute, University of Minnesota

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Mechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis. Levels of Eng determine the activation of both BMP and Wnt pathways, which are integrated downstream of Eng by phosphorylation of Smad1 by Gsk3. By interrogating Eng-dependent Wnt-mediated transcriptional changes, we identify Jdp2 as a key Eng-dependent Wnt target, sufficient to establish haematopoietic fate in early mesoderm when BMP and Wnt crosstalk is disturbed. These studies provide mechanistic insight into the integration of BMP and Wnt signalling in the establishment of haematopoietic and cardiac progenitors during embryogenesis.

Date: 2016
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DOI: 10.1038/ncomms13101

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