PUBLICATION
Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2
- Authors
- 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.
- ID
- ZDB-PUB-180905-8
- Date
- 2016
- Source
- Nature communications 7: 13101 (Journal)
- Registered Authors
- Kawakami, Yasuhiko, Tahara, Naoyuki
- Keywords
- none
- MeSH Terms
-
- Wnt3 Protein/genetics*
- Homeobox Protein Nkx-2.5/metabolism
- Cell Line
- Male
- Female
- Phosphorylation
- Animals
- Hematopoiesis/genetics*
- Hematopoiesis/physiology
- Gene Expression Regulation, Developmental
- beta Catenin/genetics
- Zebrafish
- Wnt Signaling Pathway/genetics
- Body Patterning/genetics*
- Body Patterning/physiology
- Endoglin/genetics*
- Zebrafish Proteins/genetics*
- Glycogen Synthase Kinase 3/metabolism
- Smad1 Protein/metabolism
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice
- Signal Transduction/genetics
- Bone Morphogenetic Protein 4/genetics*
- PubMed
- 27713415 Full text @ Nat. Commun.
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping