Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish.
We have examined the expression of a Hairy/E(spl)-related (Her) gene, her7, in the zebrafish and show that its expression in the PSM cycles similarly to her1 and deltaC. A decrease in her7 function generated by antisense oligonucleotides disrupts somite formation in the posterior trunk and tail, and disrupts the dynamic expression domains of her1 and deltaC, suggesting that her7 plays a role in coordinating the oscillations of neighboring cells in the presomitic mesoderm. This phenotype is reminiscent of zebrafish segmentation mutants with lesions in genes of the Delta/Notch signaling pathway, which also show a disruption of cyclic her7 expression. The interaction of HER genes with the Delta/Notch signaling system was investigated by introducing a loss of her7 function into mutant backgrounds. This leads to segmental defects more anterior than in either condition alone. Combining a decrease of her7 function with reduction of her1 function results in an enhanced phenotype that affects all the anterior segments, indicating that Her functions in the anterior segments are also partially redundant. In these animals, gene expression does not cycle at any time, suggesting that a complete loss of oscillator function had been achieved. Consistent with this, combining a reduction of her7 and her1 function with a Delta/Notch mutant genotype does not worsen the phenotype further. Thus, our results identify members of the Her family of transcription factors that together behave as a central component of the oscillator, and not as an output. This indicates, therefore, that the function of the segmentation oscillator is restricted to the positioning of segmental boundaries. Furthermore, our data suggest that redundancy between Her genes and genes of the Delta/Notch pathway is in part responsible for the robust formation of anterior somites in vertebrates.
Oates
Andrew C
AC
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. aoates@midway.uchicago.edu
Ho
Robert K
RK
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D016376:Oligonucleotides, Antisense; D051880:Receptors, Notch; D015398:Signal Transduction; D013623:Tail / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C460099:HER7 protein, zebrafish; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D051880:Receptors, Notch; D014157:Transcription Factors; D029961:Zebrafish Proteins; C064045:delta protein; C079744:her-1 protein, C elegans