Identification of genes underlying hypoxia tolerance in Drosophila by a P-element screen.
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% O(2) 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.
Department of Pediatrics, University of California-San Diego, La Jolla, California 92093, USA.
Priti
P
Azad
Dan
D
Zhou
Rachel
R
Zarndt
Gabriel G
GG
Haddad
D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D055106:Genome-Wide Association Study; D000860:Hypoxia / Q000235:genetics*; D058977:Molecular Sequence Annotation; D009928:Organ Specificity / Q000235:genetics; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C117995:osa protein, Drosophila