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Publication : Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment.

First Author  Guzman-Ayala M Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  44 Pages  15656-60
PubMed ID  15505202 Mgi Jnum  J:93446
Mgi Id  MGI:3057068 Doi  10.1073/pnas.0405429101
Citation  Guzman-Ayala M, et al. (2004) Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment. Proc Natl Acad Sci U S A 101(44):15656-60
abstractText  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 beta-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.
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