The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis.
The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis.
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Notch 基因座和遗传电路参与早期果蝇神经发生。
DOI：
10.1101/gad.4.3.464
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发表时间：
1990
影响因子：
10.5
通讯作者：
Artavanis-Tsakonas,S
中科院分区：
文献类型：
--
作者：
Xu,T;Rebay,I;Fleming,RJ;Scottgale,TN;Artavanis-Tsakonas,S
编码与哺乳动物表皮生长因子具有同源性的跨膜蛋白的Notch基因座的遗传和分子分析表明，Notch蛋白参与了果蝇胚胎神经系统分化所必需的细胞相互作用机制。利用影响蛋白质胞外结构域的两个Notch突变之间的负互补，我们试图通过寻找其产物可能与Notch蛋白相互作用的基因来剖析Notch整合的遗传电路。这种遗传筛选导致了一组令人惊讶的限制性相互作用位点的鉴定，包括Delta和mastermind。像Notch一样，这两个基因都属于一组基因座，即神经原性基因座，先前已通过影响早期神经发生的相似突变表型鉴定出这两个基因。我们通过系统地探索Notch分子和其他神经基因中特定突变之间的相互作用来扩展这些研究。此外，我们还表明，两个Notch等位基因（nd和nd 2）的分子损伤涉及细胞内结构域的变化，它们与策划突变以及影响分裂神经原性位点增强子的转导蛋白同源产物的突变发生显着相互作用。蛋白质。
The genetic and molecular analysis of the Notch locus, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, suggests that the Notch protein is involved in a cell interaction mechanism essential for the differentiation of the embryonic nervous system of Drosophila. Taking advantage of the negative complementation between two Notch mutations that affect the extracellular domain of the protein, we have tried to dissect the genetic circuitry in which Notch is integrated by searching for genes whose products may interact with the Notch protein. This genetic screen has led to the identification of a surprisingly restricted set of interacting loci, including Delta and mastermind. Like Notch, both of these genes belong to a group of loci, the neurogenic loci, which have been previously identified by virtue of their similar mutant phenotype affecting early neurogenesis. We extend these studies by systematically exploring interactions between specific mutations in the Notch molecule and the other neurogenic genes. Furthermore, we show that the molecular lesions of two Notch alleles (nd and nd2), which interact dramatically with mastermind mutations, as well as with a mutation affecting the transducin homologous product of the neurogenic locus Enhancer of split, involve changes in the intracellular domain of the protein.