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A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture

Citation

Zheng, Z and de Iongh, RU and Rathjen, PD and Rathjen, J, A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture, PL o S One, 5 pp. e12555. ISSN 1932-6203 (2010) [Refereed Article]

DOI: doi:10.1371/journal.pone.0012555

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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Development, Proliferation and Death
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Rathjen, PD (Professor Peter Rathjen)
Author:Rathjen, J (Dr Joy Rathjen)
ID Code:78720
Year Published:2010
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-07-24
Last Modified:2012-07-24
Downloads:0

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