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PTHRP/Adenylate cyclase promotes parietal whereas Wnt/β-catenin signaling promotes visceral endoderm differentiation of rat XEN cells.
MedLine Citation:
PMID:  23038778     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
During early mammalian development, primitive endoderm (PrE) is specified and segregated away from the pluripotent epiblast. At a later developmental stage, PrE forms motile parietal endoderm (PE) lying proximal to the trophectoderm, and visceral endoderm (VE) that contacts the developing epiblast and extraembryonic ectoderm. Mouse extraembryonic endoderm (XEN) cells were isolated and became widely used to study signals governing lineage specification. Rat XEN cell lines have also been derived, but were distinguished from mouse by expression of SSEA1 and Oct4. We showed here that rat XEN cells grown in the presence of a GSK3 inhibitor or overexpressing β-catenin exhibited enhanced formation of cell contacts and decreased motility. Rat XEN cells treated with BMP4 revealed similar morphological changes. Furthermore, we observed that rat XEN cells cultured with GSK3 inhibitor formed adhesion and tight junctions, and acquired bottom-top polarity, indicating the formation of VE cells. In contrast, forskolin, an activator of the cAMP pathway, induced the disruption of cell contacts in rat XEN cells. Treatment with forskolin induced the PE formation and epithelial-mesenchymal transition (EMT) in rat XEN cells. Using microarray and real-time PCR assays, we found that VE versus PE formation of rat XEN cells was correlated with change in expression levels of VE or PE marker genes. Similar to forskolin, EMT was prompted upon treatment of rat XEN cells with recombinant parathyroid hormone related peptide (PTHRP), an activator of the cAMP pathway in vivo. Taken together, our data suggest that rat XEN cells are PrE-like cells. The activation of Wnt or BMP4 pathways in rat XEN cells leads to the acquisition of VE characteristics, whereas the activation of the PTHRP/cAMP pathway leads to EMT and the formation of PE.
Authors:
Ilya Chuykin; Herbert Schulz; Kaomei Guan; Michael Bader
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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