beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation
beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation
复制标题
DOI：
10.1016/j.ydbio.2005.06.040
复制
发表时间：
2005-10-15
影响因子：
2.7
通讯作者：
Holley, SA
中科院分区：
文献类型：
--
作者：
Jülich, D;Lim, CH;Holley, SA
1996年完成的Tubingen大规模斑马鱼基因筛选确定了有序体分割所需的一组5个基因。其中4个已被分子鉴定，3个被发现编码Notch通路的成分，这是在体前中胚层（PSM）中基因表达的协调振荡所必需的，被称为分割时钟。在这里，我们展示了该组的最后一个成员beamter （bea）编码Notch配体DeltaC，我们提出并表征了两个新的等位基因，包括一个等位基因编码在第7个EGF重复中截断的蛋白质，以及一个等位基因只删除DSL结构域，这是以前证明的配体功能所必需的。然而，有趣的是，当我们过表达任何突变的deltaC mrna时，我们观察到后脑神经发生和下索形成的反胚性作用。bea/deltaC的表达在PSM中振荡，对其与PSM中其他振荡基因的振荡进行三重荧光原位分析，揭示了振荡mrna在不同振荡阶段在单个细胞中的亚细胞定位差异。aei/deltaD和bea/deltaC突变的不同之处在于它们破坏her1和deltaC振荡表达的方式。此外，我们发现双突变体在下索形成中有明显更强的缺陷，但在躯体发生或后脑神经发生中没有，这表明从遗传学上讲，两个delta可能是半冗余的，也可能是明显的，这取决于环境。(C) 2005爱思唯尔公司版权所有。
The Tubingen large-scale zebrafish genetic screen completed in 1996 identified a set of five genes required for orderly somite segmentation. Four of them have been molecularly identified and three were found to code for components of the Notch pathway, which are required for the coordinated oscillation of gene expression, known as the segmentation clock, in the presomitic mesoderm (PSM). Here, we show that the final member of the group, beamter (bea), codes for the Notch ligand DeltaC, and we present and characterize two new alleles, including one allele encoding for a protein truncated in the 7th EGF repeat and an allele deleting only the DSL domain which was previously shown to be necessary for ligand function. Interestingly however, when we over-express any of the mutant deltaC mRNAs, we observe antimorphic effects on both hindbrain neurogenesis and hypochord formation. Expression of bea/deltaC oscillates in the PSM, and a triple fluorescent in situ analysis of its oscillation in relation to that of other oscillating genes in the PSM reveals differences in subcellular localization of the oscillating mRNAs in individual cells in different oscillation phases. Mutations in aei/deltaD and bea/deltaC differ in the way they disrupt the oscillating expression of her1 and deltaC. Furthermore, we find that the double mutants have significantly stronger defects in hypochord formation but not in somitogenesis or hindbrain neurogenesis, indicating genetically that the two delta's may function either semi-redundantly or distinctly, depending upon context. (C) 2005 Elsevier Inc. All rights reserved.