11.
Germ-line cell deathThe finding that programmed cell death occurs not only in the developmentally
determined somatic cell lineage but also in the germ line of hermaphroditic worms
has initiated a host of new discoveries. The C. elegans g e r m l i n e i s t h e o n l y p ro l i f e ra t i n g
tissue in the adult animal. The distal tip cell generates germ cells and instructs them
to divide mitotically until they reach the transition zone (Seydoux and Schedl, 2001).
Here they initiate meiosis and proceed until diakinesis (Seydoux and Schedl, 2001).
Upon fertilization in the spermatheca, the oozytes resume meiosis, giving rise to
embryos (Figure 1). Gumienny et al. (1999) noticed the presence of about 0–4 germ-
cell corpses at any given time in the adult hermaphroditic germ line. Germ-cell
apoptosis is correlated with age, as the number of corpses increases with the age of
the worm (Gumienny et al., 1999). As a consequence, over 300 germ cells,
corresponding to 50% of all germ cells produced, die through programmed cell death
in an adult worm (Gumienny et al., 1999). These deaths occur only in the female
gonad in cells of the pachytene phase of meiosis I. Since these deaths occur
independently of environmental stimuli, they were termed physiologic germ cell
deaths. Interestingly, physiologic germ-cell death is dependent on the worm ras/map
kinase pathway that is needed for the commitment of meiotic pachytene cells to enter
the meiotic diplotene stage. In the absence of ras/map kinase signaling, germ-cell
d e a t h c a nn o t o c c ur. I t i s u n c l e ar w h e t h e r t h i s d e p e n d e n c y i s d ue to a d i re c t c o n n ec ti o n
of map kinase signaling with proapoptotic genes. Alternatively, the effect of map
kinase signaling might be indirect, as only cells committed to leave the pachytene via
the activation of map kinase signaling have the capacity to apoptose (Gumienny et
al., 1999). Like somatic apoptosis, physiologic germ-cell death is dependent on
ced-3and ced-4, and the engulfment of corpses requires the same set of genes as during
somatic cell death. However, the somatic cell-death trigger egl-1 is not required for
physiologic germ-cell death (Gumienny et al., 1999). Therefore, at least one
additional, germ-line-specific apoptotic trigger has been postulated, but its identity
has remained elusive.
In addition to physiologic germ-cell death, it was recently discovered that
environmental stimuli can trigger programmed germ-cell death. Infection with a
virulent form of the bacterium Salmonella typhimurium induces apoptosis in the C.
elegans germ line (Aballay and Ausubel, 2001). C. elegans is usually fed on a lawn of
E. coli, but when Aballay and Ausubel left worms with S. typhimurium as their only
food source, they observed elevated levels of germ-cell death (Aballay and Ausubel,
2001). Bacteria-induced programmed germ-cell death requires all components of the
core apoptotic pathway, including egl-1. Interestingly, worms mutant for egl-1, ced-3,
ced-4, or ced-9 (gf) die earlier when fed on S. typhimurium than their wild-type
counterparts (Aballay and Ausubel, 2001). It will be interesting to define the specific
pathways that lead to bacteria-induced apoptosis.
Genotoxic stress, such as ionizing irradiation, can also lead to programmed cell
death in C. elegans (Gartner et al., 2000). Upon irradiation, germ cells activate
PROGRAMMED CELL DEATH IN C.ELEGANS 173