Ben Abdelkhalek, H* ; Beckers, A.* ; Burkhardt, H* ; Ceolin, M* ; Rivera-Pomar, R*
    
 
    
        
The mouse homeobox gene Not is required for caudal notochord development and affected 1725 by the truncate mutation
    
    
        
    
    
        
        Genes Dev. 18, 1725-1736 (2004)
    
    
		
		
		  DOI
 DOI
		
		
		
		
		  
		
		
			 möglich sobald  bei der ZB eingereicht worden ist.
		
     
    
		
		
			
				The floating head (flh) gene in zebrafish encodes a homeodomain protein, which is essential for notochord formation along the entire body axis. flh orthologs, termed Not genes, have been isolated from chick and Xenopus, but no mammalian ortholog has yet been identified. Truncate (tc) is an autosomal recessive mutation in mouse that specifically disrupts the development of the caudal notochord. Here, we demonstrate that truncate arose by a mutation in the mouse Not gene. The truncate allele (Not(tc)) contains a point mutation in the homeobox of Not that changes a conserved Phenylalanine residue in helix 1 to a Cysteine (F20C), and significantly destabilizes the homeodomain. Reversion of F20C in one allele of homozygous tc embryonic stem (ES) cells is sufficient to restore normal notochord formation in completely ES cell-derived embryos. We have generated a targeted mutation of Not by replacing-most of the Not coding sequence, including the homeobox with the eGFP gene. The phenotype of Not(eGFP/eGFP), Not(eGFP/tc), and Not(tc/tc) embryos is very similar but slightly more severe in Not(eGFP/eGFP) than in Not(tc/tc) embryos. This confirms allelism of truncate and Not, and indicates that tc is nota complete null allele. Not expression is abolished in Foxa2 and T mutant embryos, suggesting that Not acts downstream of both genes during notochord development. This is in contrast to zebrafish embryos, in which flh interacts with nt1 (zebrafish T) in a regulatory loop and is essential for development of the entire notochord, and suggests that different genetic control circuits act in different vertebrate species during notochord formation.
			
			
				
			
		 
		
			
				
					
					Impact Factor
					Scopus SNIP
					Web of Science
Times Cited
					Scopus
Cited By
					
					Altmetric
					
				 
				
			 
		 
		
     
    
        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        notochord development; Not gene; homeodomain protein; FLOOR PLATE; ENGRAILED HOMEODOMAIN; PRIMITIVE STREAK; AXIAL MESODERM; CHICK-EMBRYO; EXPRESSION; ZEBRAFISH; XENOPUS; FATE; ORGANIZER
    
 
    
        Keywords plus
        
    
 
    
    
        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2004
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        0
    
 
    
    
        ISSN (print) / ISBN
        0890-9369
    
 
    
        e-ISSN
        1549-5477
    
 
    
        ISBN
        
    
 
    
        Bandtitel
        
    
 
    
        Konferenztitel
        
    
 
	
        Konferzenzdatum
        
    
     
	
        Konferenzort
        
    
 
	
        Konferenzband
        
    
 
     
		
    
        Quellenangaben
        
	    Band: 18,  
	    Heft: 14,  
	    Seiten: 1725-1736 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
            Reihe
            
        
 
        
            Verlag
            Cold Spring Harbor Laboratory Press
        
 
        
            Verlagsort
            
        
 
	
        
            Tag d. mündl. Prüfung
            0000-00-00
        
 
        
            Betreuer
            
        
 
        
            Gutachter
            
        
 
        
            Prüfer
            
        
 
        
            Topic
            
        
 
	
        
            Hochschule
            
        
 
        
            Hochschulort
            
        
 
        
            Fakultät
            
        
 
    
        
            Veröffentlichungsdatum
            0000-00-00
        
 
         
        
            Anmeldedatum
            0000-00-00
        
 
        
            Anmelder/Inhaber
            
        
 
        
            weitere Inhaber
            
        
 
        
            Anmeldeland
            
        
 
        
            Priorität
            
        
 
    
        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        
    
 
    
        Forschungsfeld(er)
        
    
 
    
        PSP-Element(e)
        
    
 
    
        Förderungen
        
    
 
    
        Copyright
        
    
 	
    
    
    
        Erfassungsdatum
        2004-12-31