Many genomic regions are required for normal embryonic programmed cell death in Caenorhabditis elegans

To identify genes involved in programmed cell death (PCD) in Caenorhabditis elegans, we screened a comprehensive set of chromosomal deficiencies for a lterations in the pattern of PCD throughout embryonic development. From a s et of 58 deficiencies, which collectively remove similar to 74% of the geno me, four distinct classes were identified. In class I (20 deficiencies), no significant deviation from wild type in the temporal pattern of cell corps es was observed, indicating that much of the genome does not contain zygoti c genes that perform conspicuous roles in embryonic PCD. The class II defic iencies (16 deficiencies defining at least 11 distinct genomic regions) led to no or fewer-than-normal cell corpses. Some of these cause premature cel l division arrest, probably explaining the diminution in cell corpse number ; however, others have little effect on cell proliferation, indicating that tile reduced cell corpse number is not a direct result of premature embryo nic arrest. In class III (18 deficiencies defining at least 16 unique regio ns), an excess of cell corpses was observed. The developmental stage at whi ch the extra corpses were observed varied among the class III deficiencies, suggesting the existence of genes that perform temporal-specific functions in PCD. The four deficiencies in class TV (defining at least three unique regions), showed unusually large corpses that were, ill some cases, attribu table to extremely premature arrest in cell division without a concomitant block in PCD. Deficiencies in this last class suggest that the cell death p rogram does not require normal embryonic cell proliferation to be activated and suggest that while some genes required for cell division might also be required for cell death, others are not. Most of the regions identified by these deficiencies do not contain previously identified zygotic cell death genes. There are, therefore, a substantial number of as yet unidentified g enes required for normal PCD in C. elegans.