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Title: A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture
Authors: Zheng Z. 
de Iongh R.U.
Rathjen P.D.
Rathjen J.
Keywords: bone morphogenetic protein 4
fibroblast growth factor
fibroblast growth factor 1
fibroblast growth factor 4
fibroblast growth factor 8
fibroblast growth factor
animal cell
cell culture
cell differentiation
cell lineage
controlled study
embryonic stem cell
gene expression
gene function
gene identification
genetic marker
pluripotent stem cell
primitive streak
signal transduction
cell differentiation
cell line
culture technique
gene expression regulation
prenatal development
Wistar rat
Cell Culture Techniques
Cell Differentiation
Cell Line
Embryonic Stem Cells
Fibroblast Growth Factors
Gene Expression Regulation, Developmental
Primitive Streak
Rats, Wistar
Signal Transduction
Issue Date: 2010
Citation: Zheng Z., de Iongh R.U., Rathjen P.D., Rathjen J. (2010). A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture. PLoS ONE 5 (9) : 1-13. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Embryonic stem (ES) cells hold considerable promise as a source of cells with therapeutic potential, including cells that can be used for drug screening and in cell replacement therapies. Differentiation of ES cells into the somatic lineages is a regulated process; before the promise of these cells can be realised robust and rational methods for directing differentiation into normal, functional and safe cells need to be developed. Previous in vivo studies have implicated fibroblast growth factor (FGF) signalling in lineage specification from pluripotent cells. Although FGF signalling has been suggested as essential for specification of mesoderm and endoderm in vivo and in culture, the exact role of this pathway remains unclear. Methodology/Principal Findings: Using a culture model based on early primitive ectoderm-like (EPL) cells we have investigated the role of FGF signalling in the specification of mesoderm. We were unable to demonstrate any mesoderm inductive capability associated with FGF1, 4 or 8 signalling, even when the factors were present at high concentrations, nor any enhancement in mesoderm formation induced by exogenous BMP4. Furthermore, there was no evidence of alteration of mesoderm sub-type formed with addition of FGF1, 4 or 8. Inhibition of endogenous FGF signalling, however, prevented mesoderm and favoured neural differentiation, suggesting FGF signalling was required but not sufficient for the differentiation of primitive ectoderm into primitive streak-like intermediates. The maintenance of ES cell/early epiblast pluripotent marker expression was also observed in cultures when FGF signalling was inhibited. Conclusions/Significance: FGF signalling has been shown to be required for the differentiation of primitive ectoderm to neurectoderm. This, coupled with our observations, suggest FGF signalling is required for differentiation of the primitive ectoderm into the germ lineages at gastrulation. © 2010 Zheng et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0012555
Rights: Attribution 4.0 International
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