Gal4/uas System Screening Mechanism Of Human Functional Genes And Ras Inhibition Of Apoptosis In Drosophila Eyes

Human genome sequencing has been completed. How to predict those genes function is a big challenge faced by us. Using the GAL4/UAS system, we overexpressed human genes in fly different tissues and found out genes that overexpressed in fly could cause abnormal phenotypes. By this way we did the genetic screen. Among 61 genes, 6 genes produced misexpression phenotypes in fly tissues. We system investigated one gene function and proved this is an autoimmunity related gene.This result proved this was a feasibility way to do the systematically screen and predict genes function.During this screen, we isolated a fly line that contains a spontaneous ras^KP mutation. Ras was known to deliver antiapoptotic signals by inhibition of Hid activity in the Drosophila eye. Through analysis of a newly isolated ras loss-of-function allele (ras^KP), we provide evidence that Ras also has a Hid-independent activity that likely act through the JNK pathway to inhibit apoptosis during eye development. Removal of hid only weakly suppresses the apoptosis phenotype associated with ras^KP. Inhibition of JNK pathway significantly suppresses this apoptosis phenotype. On the other hand, JNK is activated in the ras^KPeye disc. Inhibition of JNK pathway activity and overexpression of p35 in the same eye completely block apoptosis caused by ras^KP mutant. These results suggest that Ras may protect cell from apoptosis by inhibiting both the JNK and Hid activities in Drosophila eyes. Unlike in the eye, reducing Ras activity in the wing decreases cell and organ size, suggesting Ras exerts its role in a developmental content dependent manner.