PUBLICATION
            vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish
- Authors
 - Hernandez, R.E., Rikhof, H.A., Bachmann, R., and Moens, C.B.
 - ID
 - ZDB-PUB-040908-10
 - Date
 - 2004
 - Source
 - Development (Cambridge, England) 131(18): 4511-4520 (Journal)
 - Registered Authors
 - Hernandez, Rafael, Moens, Cecilia, Rikhof, Holly
 - Keywords
 - Rhombomere, Hindbrain, Retinoic acid, vhnf1, valentino, mafB, Fibroblast growth factor, hox
 - MeSH Terms
 - 
    
        
        
            
                
- Fibroblast Growth Factor 8
 - Fibroblast Growth Factor 3
 - Zebrafish Proteins/genetics
 - Zebrafish Proteins/metabolism
 - Ephrin-B2/metabolism
 - Hepatocyte Nuclear Factor 1-beta
 - Gene Expression Regulation, Developmental
 - Fibroblast Growth Factors/deficiency
 - Fibroblast Growth Factors/genetics
 - Fibroblast Growth Factors/metabolism*
 - Mosaicism/genetics
 - Animals
 - Mutation/genetics
 - Embryo, Nonmammalian/cytology
 - Embryo, Nonmammalian/embryology
 - Embryo, Nonmammalian/metabolism
 - Transcription Factors/genetics
 - Transcription Factors/metabolism*
 - Signal Transduction
 - Body Patterning
 - Nerve Tissue Proteins/genetics
 - Nerve Tissue Proteins/metabolism
 - Zebrafish/embryology*
 - Zebrafish/genetics
 - Zebrafish/metabolism*
 - Rhombencephalon/cytology
 - Rhombencephalon/embryology*
 - Rhombencephalon/metabolism*
 - MafB Transcription Factor
 - Tretinoin/metabolism*
 - DNA-Binding Proteins/genetics
 - DNA-Binding Proteins/metabolism*
 - Homeodomain Proteins/metabolism
 
 - PubMed
 - 15342476 Full text @ Development
 
            Citation
        
        
            Hernandez, R.E., Rikhof, H.A., Bachmann, R., and Moens, C.B. (2004) vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish. Development (Cambridge, England). 131(18):4511-4520.
        
    
                
                    
                        Abstract
                    
                    
                
                
            
        
        
    
        
            
            
 
    
    
        
    
    
    
        
                The vertebrate hindbrain is transiently divided along the anterior-posterior axis into seven morphologically and molecularly distinct segments, or rhombomeres, that correspond to Hox expression domains. The establishment of a proper 'hox code' is required for the development of unique rhombomere identities, including specification of neuronal fates. valentino (val), the zebrafish ortholog of mafB/Kreisler (Kr), encodes a bZip transcription factor that is required cell autonomously for the development of rhombomere (r) 5 and r6 and for activation of Hox group 3 gene expression. Recent work has demonstrated that the expression of val itself depends on three factors: retinoic acid (RA) signals from the paraxial mesoderm; fibroblast growth factor (Fgf) signals from r4; and variant hepatocyte nuclear factor 1 (vhnf1, also known as tcf2), a homeodomain transcription factor expressed posterior to the r4-5 boundary. We have investigated the interactions between these inputs onto val expression in the developing zebrafish hindbrain. We show that RA induces val expression via activation of vhnf1 expression in the hindbrain. Fgf signals from r4, acting through the MapK pathway, then cooperate with Vhnf1 to activate val expression and subsequent r5 and r6 development. Additionally, vhnf1 and val function as part of a multistep process required for the repression of r4 identity in the posterior hindbrain. vhnf1 acts largely independently of val to repress the r4 'hox code' posterior to the r4-5 boundary and therefore to block acquisition of r4-specific neuronal fates in the posterior hindbrain. However, vhnf1 is not able to repress all aspects of r4 identity equivalently. val is required downstream of vhnf1 to repress r4-like cell-surface properties, as determined by an 'Eph-ephrin code', by repressing ephrin-B2a expression in r5 and r6. The different requirements for vhnf1 and val to repress hoxb1a and ephrin-B2a, respectively, demonstrate that not all aspects of an individual rhombomere's identity are regulated coordinately.
            
    
        
        
    
    
    
                
                    
                        Genes / Markers
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Expression
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Phenotype
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mutations / Transgenics
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Human Disease / Model
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Sequence Targeting Reagents
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Fish
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Orthology
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Engineered Foreign Genes
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mapping