Genetic regulation of programmed cell death in the developing Drosophila retina

Programmed cell death (PCD) in the Drosophila eye requires the irregular chiasmC-roughest (irreC-rst) gene. Loss-of-function mutations in irreC-rst block PCD during retinal development and lead to a rough eye phenotype in the adult. To identify genes that interact with irreC-rst and may be involved in PCD, we conducted a genetic screen for dominant enhances and suppressors of the adult rough eye phenotype. We screened{09}150,000 mutagenized{09}flies and recovered 192 dominant modifiers. One complementation group of enhancers corresponded to Delta, a gene implicated previously in Drosophila retinal PCD. Several other allelic groups of modifiers were isolated on both the second and third chromosomes. Examination of retinas from homozygous mutants indicated four major phenotypic classes. Two classes exhibited pleiotrophic defects while the other two classes exhibited defects specific to the cell population that normally undergoes PCD. In addition, we screened a collected of P-element lines from the Bloomington stock center and identified a number that enhance or suppress irreC-rst [3]. These include the Drosophila, inhibitor of apoptosis protein, thread.; I have developed an in vitro culture system for pupal eye discs. This method recapitulates the pattern of programmed cell death seen in vivo. This system can be used to test the effects of a pharmacological agent on PCD in the pupal eye. Culture in caspase inhibitors block death, confirming the value of this system. A number of potential applications of this technique are discussed.; Prior evidence suggests a role for the MAPK p38 in the regulation of programmed cell death in a variety of circumstances. I used the tools available in Drosophila including the organculture system I developed to examine the role of the p38 pathway in the regulation of programmed cell death in the pupal eye. Both culture in p38 inhibitors and expression of MKK3 constructs in the eye suggest a role for the p38 pathway in the regulation of programmed cell death in the developing Drosophila eye.