"Phagocytosis of apoptotic cells is an integral part of the cell death program and an important cellular process in tissue remodeling, suppression of inflammation, and regulation of immune responses. In C. elegans, two parallel and partially redundant pathways have been identified that regulate the cell corpse engulfment, with
ced-1,
ced-7,
ced-6,
dyn-1 acting in one pathway, and
psr-1,
ced-2,
ced-5,
ced-12 and
ced-10 in the other. PSR-1, the C. elegans phosphatidylserine receptor (PSR) likely functions to transduce the PS engulfment signal through direct interaction via its cytoplasmic tail with CED-5 and CED-12(1). However, PSR-1 is unlikely to be the only engulfment receptor in this pathway since the
psr-1 deletion mutant (
tm469) displays much weaker engulfment defect than that of the
ced-2,
ced-5,
ced-12 and
ced-10 mutants. In order to identify additional factors that may function redundantly with
psr-1 to promote cell corpse engulfment, we carried out a large-scale
psr-1 enhancer screen to isolate mutations that can enhance the engulfment defect of the
psr-1 (
tm469) mutant.From a screen of 30,000 C. elegans haploid genomes, we isolated a recessive mutation,
qx16, which contains persistent cell corpses at late embryonic stages. Examination of
qx16 mutant indicated that significantly higher numbers of cell corpses were accumulated in
qx16 animals than in wild-type embryos at every embryonic stage. Furthermore, 4-dimensional microscopy analysis revealed that this increase of embryonic cell corpses in
qx16 mutant is caused by defects in cell corpse engulfment. Double mutants between
qx16 and mutations in the genes from the two parallel engulfment pathways are being constructed. We are currently in the process of cloning the gene affected in the
qx16 mutant and performing further genetic analyses to understand its function in cell corpse engulfment. We will report our progress during the meeting.1. Wang, X.C., Wu, Y.C., Fadok, V., Lee, M.C., Gengyo-Ando, K., Cheng, L.C., Ledwich, D., Hsu, P.K., Chen, J.Y., Chou, B.K., Henson, P., Mitani, S., and Xue, D. (2003). Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12. Science 302, 1563-1566"