c-jun regulation and function in the developing hindbrain.
Hindbrain development is a well-characterised segmentation process in vertebrates. The bZip transcription factor MafB/kreisler is specifically expressed in rhombomeres (r) 5 and 6 of the developing vertebrate hindbrain and is required for proper caudal hindbrain segmentation. Here, we provide evidence that the mouse protooncogene c-jun, which encodes a member of the bZip family, is coexpressed with MafB in prospective r5 and r6. Analysis of mouse mutants suggests that c-jun expression in these territories is dependent on MafB but independent of the zinc-finger transcription factor Krox20, another essential determinant of r5 development. Loss- and gain-of-function studies, performed in mouse and chick embryos, respectively, demonstrate that c-Jun participates, together with MafB and Krox20, in the transcriptional activation of the Hoxb3 gene in r5. The action of c-Jun is likely to be direct, since c-Jun homodimers and c-Jun/MafB heterodimers can bind to essential regulatory elements within the transcriptional enhancer responsible for Hoxb3 expression in r5. These data indicate that c-Jun acts both as a downstream effector and a cofactor of MafB and belongs to the complex network of factors governing hindbrain patterning.
Mechta-Grigoriou
Fatima
F
Unité Expression génétique et maladies, CNRS URA 1644, Institut Pasteur 25, rue du Docteur Roux, 75724 15, Paris Cedex, France. fmechta@pasteur.fr
Giudicelli
Francois
F
Pujades
Cristina
C
Charnay
Patrick
P
Yaniv
Moshe
M
D000818:Animals; D030161:Avian Proteins; D001665:Binding Sites / Q000235:genetics; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D051767:Early Growth Response Protein 2; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016758:Genes, jun; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D051258:MafB Transcription Factor; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D015513:Oncogene Proteins / Q000378:metabolism; D011247:Pregnancy; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D029867:Xenopus Proteins / Q000235:genetics
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D018398:Homeodomain Proteins; C078105:Hox 2.7 protein, Xenopus; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C091157:maf-B protein, chicken