title: Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2.
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.
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: June
authors.initials: J
authors.lastname: Baik
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magli
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tahara
authors.affiliation: Regerative Biology, Morgridge Institute for Research, Madison, Wisconsin 53715, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Swanson
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Luciene
authors.initials: L
authors.lastname: Borges
authors.affiliation: Regerative Biology, Morgridge Institute for Research, Madison, Wisconsin 53715, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Regerative Biology, Morgridge Institute for Research, Madison, Wisconsin 53715, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Rita C R
authors.initials: RC
authors.lastname: Perlingeiro
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D002460:Cell Line; D000071063:Endoglin / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D051898:Smad1 Protein / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D060508:Wnt3 Protein / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: D055415:Bone Morphogenetic Protein 4; D000071063:Endoglin; D000072576:Homeobox Protein Nkx-2.5; D051898:Smad1 Protein; D060508:Wnt3 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; D038362:Glycogen Synthase Kinase 3