Redeker, C.* ; Schuster-Gossler, K.* ; Kremmer, E. ; Gossler, A.*
     
 
    
        
Normal development in mice over-expressing the intracellular domain of DLL1 argues against reverse signaling by DLL1 in vivo.
    
    
        
    
    
        
        PLoS ONE 8:e79050 (2013)
    
    
    
		
		
			
				The Notch signaling pathway mediates the direct communication between adjacent cells and regulates multiple developmental processes. Interaction of the Notch receptor with its ligands induces the liberation of the intracellular portion of Notch (NICD) referred to as regulated intramembraneous proteolysis (RIP). NICD translocates to the nucleus, and by complexing with the DNA binding protein RBPjκ and other cofactors activates transcription of bHLH genes. RIP-like processing of various mammalian Notch ligands (DLL1, JAG1 and JAG2) and the translocation of their intracellular domains (ICDs) to the nucleus has also been observed. These observations together with effects of over-expressed ligand ICDs in cultured cells on cell proliferation, differentiation, and Notch activity and target gene expression have led to the idea that the intracellular domains of Notch ligands have signaling functions. To test this hypothesis in vivo we have generated ES cells and transgenic mice that constitutively express various versions of the intracellular domain of mouse DLL1. In contrast to other cell lines, expression of DICDs in ES cells did not block proliferation or stimulate neuronal differentiation. Embryos with ubiquitous DICD expression developed to term without any apparent phenotype and grew up to viable and fertile adults. Early Notch-dependent processes or expression of selected Notch target genes were unaltered in transgenic embryos. In addition, we show that mouse DICD enters the nucleus inefficiently. Collectively, our results argue against a signaling activity of the intracellular domain of DLL1 in mouse embryos in vivo.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Embryonic Stem-cells ; Notch Ligand Delta1 ; Egf-like Repeats ; Nucleotide-sequence ; Drosophila-melanogaster ; Transmembrane Protein ; Escherichia-coli ; Progenitor Cells ; Gene-expression ; Gamma-secretase
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2013
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2013
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
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	    Band: 8,  
	    Heft: 10,  
	    Seiten: ,  
	    Artikelnummer: e79050 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Public Library of Science (PLoS)
        
 
        
            Verlagsort
            Lawrence, Kan.
        
 
	
        
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        Peer reviewed
    
 
     
    
        POF Topic(s)
        30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
    
 
    
        Forschungsfeld(er)
        Immune Response and Infection
    
 
    
        PSP-Element(e)
        G-501793-001
    
 
    
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        Erfassungsdatum
        2013-11-06