a requirement for fgf signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture要求fgf信号形成的原始streak-like中间体在文化原始外胚层.pdfVIP

A Requirement for FGF Signalling in the Formation of Primitive Streak-Like Intermediates from Primitive Ectoderm in Culture 1 2 1 1 Zhiqiang Zheng , Robb U. de Iongh , Peter D. Rathjen , Joy Rathjen * 1 Department of Zoology, University of Melbourne, Parkville, Australia, 2 Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia 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 favoure