Drosophila growth and development in the absence of dMyc and dMnt
Drosophila growth and development in the absence of dMyc and dMnt
复制标题
DOI：
10.1016/j.ydbio.2007.12.026
复制
发表时间：
2008-03-15
影响因子：
2.7
通讯作者：
Eisenman, Robert N.
中科院分区：
文献类型：
--
作者：
Pierce, Sarah B.;Yost, Cynthia;Eisenman, Robert N.
MYC癌蛋白是哺乳动物细胞生长和增殖的重要调节因子。在果蝇中，由dm基因编码的Myc(DMyc)的单一同源基因影响组织的大小以及有丝分裂细胞和内复制细胞的生长。DIN的零突变会导致幼虫发育早期内复制减弱和生长停滞。果蝇还含有哺乳动物Mad/Mnt转录抑制蛋白(DMnt)的单一同源基因，被认为可以拮抗dMyc功能。在这里，我们表明，与dMyc单一突变体相比，同时缺乏dMyc和dMnt的动物显示出更高的存活率，生长明显更大，发育更深入。我们观察到在这些双重突变体中，幼虫组织的内复制和生长增加，成像盘的生长不成比例。基因表达分析表明，dMye的缺失导致核糖体生物发生和蛋白质合成所需基因的表达减少。DMnt的额外丢失部分挽救了少量dMyc和dMnt基因的表达，这些基因主要参与rRNA的合成和处理。我们的结果表明，在幼虫发育过程中，dMnt的抑制通常被dMyc的激活所覆盖。因此，DIN缺失表型的严重性可能是由于dMnt对细胞和生物生长至关重要的基因子集的非对抗性抑制。令人惊讶的是，在没有dMyc和dMnt的情况下，可以出现相当大的增长和发展。(C)2007 Elsevier Inc.保留所有权利。
Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in din results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMye leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the din null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt. (C) 2007 Elsevier Inc. All rights reserved.