Document Detail

Distinct GATA6- and laminin-dependent mechanisms regulate endodermal and ectodermal embryonic stem cell fates.
MedLine Citation:
PMID:  15456727     Owner:  NLM     Status:  MEDLINE    
This study investigates the establishment of alternative cell fates during embryoid body differentiation when ES cells diverge into two epithelia simulating the pre-gastrulation endoderm and ectoderm. We report that endoderm differentiation and endoderm-specific gene expression, such as expression of laminin 1 subunits, is controlled by GATA6 induced by FGF. Subsequently, differentiation of the non-polar primitive ectoderm into columnar epithelium of the epiblast is induced by laminin 1. Using GATA6 transformed Lamc1-null endoderm-like cells, we demonstrate that laminin 1 exhibited by the basement membrane induces epiblast differentiation and cavitation by cell-to-matrix/matrix-to-cell interactions that are similar to the in vivo crosstalk in the early embryo. Pharmacological and dominant-negative inhibitors reveal that the cell shape change of epiblast differentiation requires ROCK, the Rho kinase. We also show that pluripotent ES cells display laminin receptors; hence, these stem cells may serve as target for columnar ectoderm differentiation. Laminin is not bound by endoderm derivatives; therefore, the sub-endodermal basement membrane is anchored selectively to the ectoderm, conveying polarity to its assembly and to the differentiation induced by it. Unique to these interactions is their flow through two cell layers connected by laminin 1 and their involvement in the differentiation of two epithelia from the same stem cell pool: one into endoderm controlled by FGF and GATA6; and the other into epiblast regulated by laminin 1 and Rho kinase.
Li Li; Esther Arman; Peter Ekblom; David Edgar; Patricia Murray; Peter Lonai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-29
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  131     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-15     Completed Date:  2004-12-23     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  5277-86     Citation Subset:  IM    
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
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MeSH Terms
Basement Membrane / metabolism,  secretion
Cell Differentiation
Cell Polarity
Cells, Cultured
DNA-Binding Proteins / metabolism*
Ectoderm / cytology*,  metabolism
Embryo, Mammalian / cytology*,  embryology,  metabolism*
Embryo, Nonmammalian*
Endoderm / cytology*,  metabolism
Epithelial Cells / cytology,  metabolism
Extracellular Matrix / metabolism
Fibroblast Growth Factors / metabolism
GATA6 Transcription Factor
Intracellular Signaling Peptides and Proteins
Laminin / genetics,  metabolism*
Pluripotent Stem Cells / cytology,  metabolism
Protein-Serine-Threonine Kinases / metabolism
Receptors, Fibroblast Growth Factor / antagonists & inhibitors,  genetics,  metabolism
Receptors, Laminin / metabolism
Signal Transduction
Stem Cells / cytology*,  metabolism
Tissue Culture Techniques
Transcription Factors / metabolism*
rho GTP-Binding Proteins / metabolism
rho-Associated Kinases
Reg. No./Substance:
0/DNA-Binding Proteins; 0/GATA6 Transcription Factor; 0/Intracellular Signaling Peptides and Proteins; 0/Laminin; 0/Receptors, Fibroblast Growth Factor; 0/Receptors, Laminin; 0/Transcription Factors; 0/laminin 1; 62031-54-3/Fibroblast Growth Factors; EC Kinases; EC Kinases; EC GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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