Identification of genes underlying hypoxia tolerance in Drosophila by a P-element screen.
Identification of genes underlying hypoxia tolerance in Drosophila by a P-element screen.
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DOI：
10.1534/g3.112.003681
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Haddad GG
中科院分区：
文献类型：
--
作者：
Azad P;Zhou D;Zarndt R;Haddad GG
缺氧发生在生理条件下（例如高海拔）或病理状态下（例如缺血）。我们的研究重点是了解的分子机制，导致适应和生存或损伤的缺氧应激使用果蝇作为模型系统。为了鉴定参与耐缺氧的基因，我们筛选了适用于果蝇所有染色体的P-SNP-元件插入系。我们筛选了在5%O2条件下发育的胚胎的羽化率和在相同的低氧环境中羽化后一周存活的成蝇数量。在筛选的2187个株系中，有44个代表44个基因的P元件株系在低氧条件下的羽化率（>70%）显著高于对照（>70%）。这些候选基因的分子功能包括细胞周期调控、DNA或蛋白质结合、GTP结合活性和转录调节因子。此外，通过对这些基因的通路分析，发现它们参与了Notch、Wnt、JNK和Hedgehog等多种通路。特别是，我们发现44个候选基因中有20个与Notch信号通路相关，强烈表明该通路是果蝇耐缺氧所必需的。利用UAS/RNAi-Gal 4系统，我们发现与Wnt和Notch通路相关的osa和Notch调节因子lqf等基因在果蝇缺氧条件下的生存和发育中起重要作用。基于这些结果和我们以前的研究，我们得出结论，耐缺氧是一个多基因性状，包括Notch途径。
Hypoxia occurs in physiologic conditions (e.g. high altitude) or during pathologic states (e.g. ischemia). Our research is focused on understanding the molecular mechanisms that lead to adaptation and survival or injury to hypoxic stress using Drosophila as a model system. To identify genes involved in hypoxia tolerance, we screened the P-SUP P-element insertion lines available for all the chromosomes of Drosophila. We screened for the eclosion rates of embryos developing under 5% O2 condition and the number of adult flies surviving one week after eclosion in the same hypoxic environment. Out of 2187 lines (covering ∼1870 genes) screened, 44 P-element lines representing 44 individual genes had significantly higher eclosion rates (i.e. >70%) than those of the controls (i.e. ∼7–8%) under hypoxia. The molecular function of these candidate genes ranged from cell cycle regulation, DNA or protein binding, GTP binding activity, and transcriptional regulators. In addition, based on pathway analysis, we found these genes are involved in multiple pathways, such as Notch, Wnt, Jnk, and Hedgehog. Particularly, we found that 20 out of the 44 candidate genes are linked to Notch signaling pathway, strongly suggesting that this pathway is essential for hypoxia tolerance in flies. By employing the UAS/RNAi-Gal4 system, we discovered that genes such as osa (linked to Wnt and Notch pathways) and lqf (Notch regulator) play an important role in survival and development under hypoxia in Drosophila. Based on these results and our previous studies, we conclude that hypoxia tolerance is a polygenic trait including the Notch pathway.
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DOI：
10.1126/science.1166175
发表时间：
2009-01-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anderson LL;Mao X;Scott BA;Crowder CM
通讯作者：
Crowder CM
影响因子：
3.7
作者：
Azad P;Zhou D;Russo E;Haddad GG
通讯作者：
Haddad GG
影响因子：
13.3
作者：
Csikos, Gyoergy;Lippai, Monika;Sass, Miklos
通讯作者：
Sass, Miklos
影响因子：
2.7
作者：
KONRAD, L;BECKER, G;GATEFF, E
通讯作者：
GATEFF, E
影响因子：
3.3
作者：
Armstrong, JA;Sperling, AS;Tamkun, JW
通讯作者：
Tamkun, JW