Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2
- Baik, J., Magli, A., Tahara, N., Swanson, S.A., Koyano-Nakagawa, N., Borges, L., Stewart, R., Garry, D.J., Kawakami, Y., Thomson, J.A., Perlingeiro, R.C.
- Nature communications 7: 13101 (Journal)
- Registered Authors
- Kawakami, Yasuhiko, Tahara, Naoyuki
- MeSH Terms
- Body Patterning/genetics*
- Body Patterning/physiology
- Bone Morphogenetic Protein 4/genetics*
- Cell Line
- Gene Expression Regulation, Developmental
- Glycogen Synthase Kinase 3/metabolism
- Homeobox Protein Nkx-2.5/metabolism
- Mice, Inbred C57BL
- Mice, Transgenic
- Signal Transduction/genetics
- Smad1 Protein/metabolism
- Wnt Signaling Pathway/genetics
- Wnt3 Protein/genetics*
- Zebrafish Proteins/genetics*
- beta Catenin/genetics
- 27713415 Full text @ Nat. Commun.
Baik, J., Magli, A., Tahara, N., Swanson, S.A., Koyano-Nakagawa, N., Borges, L., Stewart, R., Garry, D.J., Kawakami, Y., Thomson, J.A., Perlingeiro, R.C. (2016) Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2. Nature communications. 7:13101.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes