While many genes involved in the execution of cell death have been identified, the mechanisms that control the commitment of specific cells to undergo programmed cell death are poorly understood. To identify genes that act in cell-death specification, we performed a screen for hermaphrodites in which the male-specific CEM neurons, which die during normal hermaphrodite development but survive in males, fail to die. The reporter
pkd-2::gfp (kindly provided by Maureen Barr and Paul Sternberg) expresses in the CEMs of males and in the CEMs of hermaphrodites defective in programmed cell death. Using
pkd-2::gfp as a marker for CEM survival, we screened 60,000 mutagenized haploid genomes and recovered at least 154 independent mutations that cause CEM survival, including at least 42 alleles of known cell-death genes and 64 mutations that cause sexual transformation.Three mutations from this screen,
n3713,
n3714, and
n3720, semidominantly cause CEM survival in hermaphrodites but cause no other obvious defects in programmed cell death or sex determination. CEM survival caused by these mutations is not affected by loss of the fem genes, the most downstream genes required for masculinization, indicating that this gene may act downstream of sex determination. The
n3714 phenotype of CEM survival is not affected by a duplication covering the locus, indicating
n3714 causes increased wild-type function or altered function.In a screen for suppressors of
n3714, we found one mutation,
n4111, that is tightly linked to
n3714 and dominantly suppresses the dominant CEM survival phenotype of
n3714. In contrast to
n3714 hermaphrodites, which inappropriately have surviving CEMs,
n4111 n3714 males inappropriately lack CEMs. The CEMs of
n4111 n3714 males are restored by mutations that prevent programmed cell death but not by a null mutation in
tra-1, a gene required for feminization and the most downstream gene in the sex-determination pathway. Other deaths and sexually dimorphic characteristics are not affected by
n4111 n3714.
n4111 is a nonsense mutation in the BarH class homeodomain gene
ceh-30.
n3713,
n3714, and
n3720 are mutations in an evolutionarily conserved TRA-1 binding site in an intron of
ceh-30. We propose that
ceh-30 is specifically required for CEM survival in males and that in hermaphrodites
ceh-30 is prevented from protecting the CEMs by direct transcriptional repression by TRA-1. It remains to be determined how
ceh-30 protects the CEMs and to what extent this cell-type specific anti-apoptotic function of
ceh-30 is shared by BarH class homeodomain genes in other organisms.