Nodal Protein Processing and Fibroblast Growth Factor 4 Synergize to Maintain a Trophoblast Stem Cell Microenvironment

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,...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-11, Vol.101 (44), p.15656-15660
Main Authors: Guzman-Ayala, Marcela, Ben-Haim, Nadav, Beck, Séverine, Constam, Daniel B., Anderson, Kathryn V.
Format: Article
Language:English
Subjects:
Alleles
Animals
Biological Sciences
Biology
Cell Differentiation
Cell growth
Embryonic stem cells
Embryos
Female
Fibroblast Growth Factor 4
Fibroblast growth factors
Fibroblast Growth Factors - genetics
Furin - deficiency
Furin - genetics
Furin - metabolism
Gene Expression - drug effects
Giant cells
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Biological
Nodal Protein
Physical growth
Pregnancy
Proprotein Convertases
Protein Processing, Post-Translational
Proteins
Proto-Oncogene Proteins - genetics
Receptors
Recombinant Proteins - pharmacology
Serine Endopeptidases - deficiency
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Tissue Culture Techniques
Transcription factors
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta - pharmacology
Trophoblasts
Trophoblasts - cytology
Trophoblasts - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0405429101