Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: A novel role for γ-secretase in the formation of primitive streak-like intermediates from ES cells in culture
Other Titles: A novel role for gamma-secretase in the formation of primitive streak-like intermediates from ES cells in culture
Author: Hughes, J.
Dodge, N.
Rathjen, P.
Rathjen, J.
Citation: Stem Cells, 2009; 27(12):2941-2951
Publisher: Alphamed Press
Issue Date: 2009
ISSN: 1066-5099
Statement of
James N. Hughes, Natasha Dodge, Peter D. Rathjen and Joy Rathjen
Abstract: Υ-Secretase is a membrane-associated protease with multiple intracellular targets, a number of which have been shown to influence embryonic development and embryonic stem (ES) cell differentiation. This paper describes the use of the Υ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) to evaluate the role of Υ- secretase in the differentiation of pluripotent stem cells to the germ lineages. The addition of DAPT did not prevent the formation of primitive ectoderm-like cells from ES cells in culture. In contrast, the addition of DAPT during primitive ectoderm-like cell differentiation interfered with the ability of both serum and BMP4 to induce a primitive streak-like intermediate and resulted in the preferential formation of neurectoderm. Similarly, DAPT reduced the formation of primitive streak-like intermediates from differentiating human ES cells; the culture conditions used resulted in a population enriched in human surface ectoderm. These data suggest that Υ-secretase may form part of the general pathway by which mesoderm is specified within the primitive streak. The addition of an E-cadherin neutralizing antibody was able to partially reverse the effect of DAPT, suggesting that DAPT may be preventing the formation of primitive streak-like intermediates and promoting neurectoderm differentiation by stabilizing E-cadherin and preventing its proteolysis.
Keywords: Embryonic stem cell
Primitive streak
Rights: Copyright © 2009 AlphaMed Press
DOI: 10.1002/stem.218
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.