Oates Andrew C, Ho Robert K
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Development. 2002 Jun;129(12):2929-46. doi: 10.1242/dev.129.12.2929.
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.
我们检测了斑马鱼中一个与Hairy/E(spl)相关的（Her）基因her7的表达情况，结果表明它在体节中胚层（PSM）的表达与her1和deltaC类似呈周期性变化。反义寡核苷酸导致的her7功能降低会破坏后躯干和尾部的体节形成，并扰乱her1和deltaC的动态表达域，这表明her7在协调前体中胚层相邻细胞的振荡中发挥作用。这种表型让人联想到Delta/Notch信号通路基因有损伤的斑马鱼体节分割突变体，它们也表现出her7周期性表达的破坏。通过在突变背景中引入her7功能缺失来研究HER基因与Delta/Notch信号系统的相互作用。这导致的节段缺陷比单独任何一种情况都更靠前。将her7功能降低与her1功能降低相结合会导致一种影响所有前部体节的增强表型，这表明Her在前部体节中的功能也部分冗余。在这些动物中，基因表达在任何时候都不会循环，这表明已经实现了振荡器功能的完全丧失。与此一致的是，将her7和her1功能降低与Delta/Notch突变基因型相结合并不会使表型进一步恶化。因此，我们的结果确定了转录因子Her家族的成员共同作为振荡器的核心组成部分，而不是输出部分。因此，这表明体节分割振荡器的功能仅限于节段边界的定位。此外，我们的数据表明Her基因与Delta/Notch信号通路基因之间的冗余部分地促成了脊椎动物前部体节的稳健形成。
