PUBLICATION
FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway
- Authors
- Pouget, C., Peterkin, T., Simões, F.C., Lee, Y., Traver, D., Patient, R.
- ID
- ZDB-PUB-170214-263
- Date
- 2014
- Source
- Nature communications 5: 5588 (Journal)
- Registered Authors
- Lee, Yoonsung, Patient, Roger K., Peterkin, Tessa, Traver, David
- Keywords
- Cell signalling, Haematopoietic stem cells
- MeSH Terms
-
- Signal Transduction
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Mesoderm/metabolism
- Animals
- Stem Cell Niche
- Aorta/metabolism
- Hematopoietic Stem Cells/metabolism*
- Bone Morphogenetic Protein 4/genetics*
- Bone Morphogenetic Protein 4/metabolism
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism
- Gene Expression Regulation, Developmental/genetics*
- Cell Differentiation*
- Fibroblast Growth Factors/metabolism*
- Endothelium, Vascular/metabolism*
- PubMed
- 25429520 Full text @ Nat. Commun.
Citation
Pouget, C., Peterkin, T., Simões, F.C., Lee, Y., Traver, D., Patient, R. (2014) FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway. Nature communications. 5:5588.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping