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Nodal Protein Processing and Fibroblast Growth Factor 4 Synergize to Maintain a Trophoblast Stem Cell Microenvironment
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Nodal Protein Processing and Fibroblast Growth Factor 4 Synergize to Maintain a Trophoblast Stem Cell Microenvironment
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Journal Article
Nodal Protein Processing and Fibroblast Growth Factor 4 Synergize to Maintain a Trophoblast Stem Cell Microenvironment
2004
Overview
Before implantation in the uterus, mammalian embryos set aside trophoblast stem cells that are maintained in the extraembryonic ectoderm (ExE) during gastrulation to generate the fetal portion of the placenta. Their proliferation depends on diffusible signals from neighboring cells in the epiblast, including fibroblast growth factor 4 (Fgf4). Here, we show that Fgf4 expression is induced by the transforming growth factor β-related protein Nodal. Together with Fgf4, Nodal also acts directly on neighboring ExE to sustain a microenvironment that inhibits precocious differentiation of trophoblast stem cells. Because the ExE itself produces the proteases Furin and PACE4 to activate Nodal, it represents the first example, to our knowledge, of a stem cell compartment that actively maintains its own microenvironment.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Biology
/ Embryos
/ Female
/ Fibroblast Growth Factors - genetics
/ Gene Expression - drug effects
/ Mice
/ Protein Processing, Post-Translational
/ Proteins
/ Proto-Oncogene Proteins - genetics
/ Recombinant Proteins - pharmacology
/ Serine Endopeptidases - deficiency
/ Serine Endopeptidases - genetics
/ Serine Endopeptidases - metabolism
/ Transforming Growth Factor beta - genetics
/ Transforming Growth Factor beta - metabolism
