48
B. Conradt
3.8 Programmed Cell Death Is Initiated
by Two Independent Pathways in C. elegans
Programmed cell death in C. elegans occurs not only in somatic tissues
during C. elegans embryonic and postembryonic development but also
in the germ line of adult hermaphrodites (Sulston 1988; Hengartner
1997b). A large number of germ cells, possibly more than 50% of all
germ cells formed, undergo programmed cell death. The number of
cell-death events in this tissue appears to increase with the age of the
animal and seems to depend on the availability of food which suggests
that the programmed cell-death process in the germ line might be
regulated or at least influenced by extra-cellular, cell non-autonomous
signals (SuIston 1988).
In hermaphrodites carrying loss-of-function mutations in either ced4 or ced-3, programmed cell death in the germ line is blocked (Hengartner 1997b). This suggests that ced-4 and ced-3 are required for killing
not only in the soma but also in the germ line. Loss-of-function mutations in ced-9 cause ectopic cell death resulting in embryonic lethality.
However, ced-9 loss-of-function progeny of hermaphrodites that are
heterozygous for a ced-9 loss-of-function mutation are viable due to
maternal rescue. These ced-9 loss-of-function animals develop into
adults with low fertility as a result of the increased programmed cell
death of germ cells. This suggests that ced-9 acts as a cell-death inhibitor also in the germ line (Hengartner 1997b). The gain-of-function
mutation in ced-9, which blocks programmed cell death in the soma,
however, does not block programmed cell death in the germ line. This
suggests that differences exist in the way that programmed cell death is
initiated in the soma and in the germ line. This is supported by the
finding that the egl-l gene, which is required for programmed cell death
in the soma just like ced-4 and ced-3 are, is not involved in programmed
cell death in the germ line (Conradt and Horvitz 1998).
egl-l, hence, is not the only initiator of programmed cell death in C.
elegans. Instead, two independent pathways appear to initiate programmed cell death in this organism: an egl- J -dependent pathway that
functions in the soma and an egl-l-independent pathway that acts in the
germ line (Fig. 4). So far, there are no hints as to the nature of the
egl-l-independent pathway except that it might involve the transduction
of an extracellular signal. Considering, however, that ced-9 is also
B. Conradt
3.8 Programmed Cell Death Is Initiated
by Two Independent Pathways in C. elegans
Programmed cell death in C. elegans occurs not only in somatic tissues
during C. elegans embryonic and postembryonic development but also
in the germ line of adult hermaphrodites (Sulston 1988; Hengartner
1997b). A large number of germ cells, possibly more than 50% of all
germ cells formed, undergo programmed cell death. The number of
cell-death events in this tissue appears to increase with the age of the
animal and seems to depend on the availability of food which suggests
that the programmed cell-death process in the germ line might be
regulated or at least influenced by extra-cellular, cell non-autonomous
signals (SuIston 1988).
In hermaphrodites carrying loss-of-function mutations in either ced4 or ced-3, programmed cell death in the germ line is blocked (Hengartner 1997b). This suggests that ced-4 and ced-3 are required for killing
not only in the soma but also in the germ line. Loss-of-function mutations in ced-9 cause ectopic cell death resulting in embryonic lethality.
However, ced-9 loss-of-function progeny of hermaphrodites that are
heterozygous for a ced-9 loss-of-function mutation are viable due to
maternal rescue. These ced-9 loss-of-function animals develop into
adults with low fertility as a result of the increased programmed cell
death of germ cells. This suggests that ced-9 acts as a cell-death inhibitor also in the germ line (Hengartner 1997b). The gain-of-function
mutation in ced-9, which blocks programmed cell death in the soma,
however, does not block programmed cell death in the germ line. This
suggests that differences exist in the way that programmed cell death is
initiated in the soma and in the germ line. This is supported by the
finding that the egl-l gene, which is required for programmed cell death
in the soma just like ced-4 and ced-3 are, is not involved in programmed
cell death in the germ line (Conradt and Horvitz 1998).
egl-l, hence, is not the only initiator of programmed cell death in C.
elegans. Instead, two independent pathways appear to initiate programmed cell death in this organism: an egl- J -dependent pathway that
functions in the soma and an egl-l-independent pathway that acts in the
germ line (Fig. 4). So far, there are no hints as to the nature of the
egl-l-independent pathway except that it might involve the transduction
of an extracellular signal. Considering, however, that ced-9 is also