The CEMs (cephalic companion neurons) are four sexually dimorphic neurons located bilaterally between the two bulbs of the pharynx. The CEMs are sexually dimorphic as a result of programmed cell death: they are born around 320 min after the first cell division in both males and hermaphrodites and show signs of differentiation before being specifically removed in hermaphrodites about 150 min later. The death of the CEMs in hermaphrodites is dependent on the central programmed cell death pathway. To identify factors involved in the regulation of the sex-specific death of the CEMs, a screen for mutations that cause the inappropriate death of the CEMs was carried out using masculinized
sel-10(
n1077gf) hermaphrodites in which the CEMs survive. From this screen, three mutations were isolated that are discussed here:
bc151,
bc155, and
bc159. Any one of these mutations results in the absence of CEMs in
sel-10(
n1077gf) hermaphrodites, as well ashim-5
(e1490) males. We determined that
bc151 is a new allele of
unc-86, which encodes a POU homeodomain transcription factor, previously implicated in neuronal specification including the specification of the CEMs. Furthermore, we determined that
bc155 is a mutation in the gene
lrs-1, which encodes a leucine tRNA synthetase, and that
bc159is a mutation in the gene W08A12.1, which encodes a novel, uncharacterized protein with a P-loop motif and limited sequence similarity to the human serine/threonine-protein kinase and proto-oncoprotein PIM1. Through lineaging experiments, we found that the lack of CEMs in
bc151,
bc155 and
bc159 mutants is not a result of inappropriate programmed cell death, but a defect in CEM specification and/or differentiation. This result was confirmed by the observation that in the
ced-3(
n717) background, in which programmed cell death is blocked in general, differentiated CEMs are not observed in
bc151,
bc155, orbc159 mutants. Moreover, the defect in
bc151,
bc155 and
bc159mutants appears to be CEM specific, as other cells in the CEM lineage do not seem to be affected. The death of the CEMs in hermaphrodites is dependent on the gene
egl-1, which encodes a pro-apoptotic member of the BCL2 family of proteins. In males in which the CEMs survive,
egl-1 transcription is repressed by the BarH homeodomain transcription factor CEH-30. We are currently focusing our efforts on determining where
unc-86,
lrs-1 and W08A12.1 act with respect to the
ceh-30 and
egl-1 genes.