Programmed Cell Death and Its Regulation in C. elegans
37
1997). The sequence of its genome has just been completed and represents the first sequenced genome of a multicellular organism (The C.
elegans Sequencing Consortium 1998). Furthermore, the analysis of
complex biological processes in C. elegans is greatly facilitated by the
fact that the development of this organism occurs in an essentially
invariant manner. The availability of the complete embryonic and
postembryonic somatic cell lineage of C. elegans (Sulston and Horvitz
1977; Sulston et al. 1983) allows an analysis of various processes at
single cell resolution.
During the development of a C. elegans hermaphrodite a total of
1090 somatic cells are formed. Exactly 131 out of these 1090 cells are
eliminated again by a process which, at the morphological level, is
reminiscent of the programmed cell-death process observed in higher
organisms: the dying cells round up and shrink, the cytoplasm and
chromatin condense and eventually the cell corpses are engulfed and
phagocytosed by neighboring cells (Robertson and Thomson 1982).
These programmed cell-death events are determined by cell lineage and
occur in a cell-autonomous manner (Sulston and Horvitz 1977; Sulston
et al. 1983). Programmed cell death in the C. elegans soma can therefore
be regarded as a form of terminal differentiation or as a cell fate. Having
the knowledge of which cells undergo programmed cell death in C.
elegans and when and where this happens, allows a systematic analysis
of the cell-death process at the genetic level in this organism.
3.3 A Genetic Pathway Underlies the Process
of Programmed Cell Death
U sing a genetic approach, mutations have been isolated that block most
if not all somatic programmed cell-death events in C. elegans (reviewed
by Ellis et al. 1991 b; Metzstein et al. 1998). Animals carrying these
mutations have up to 131 extra somatic cells but otherwise develop into
healthy, fertile adults. The identification of cell-death-defective or ced
mutants in C. elegans demonstrated for the first time that the process of
programmed cell death has a genetic basis and that it is the result of the
action of a set of specific genes.
The genetically identified mutations define three genes, ced-3, ced-4,
and ced-9. Loss-of-function mutations in ced-3 or ced-4 block pro-
37
1997). The sequence of its genome has just been completed and represents the first sequenced genome of a multicellular organism (The C.
elegans Sequencing Consortium 1998). Furthermore, the analysis of
complex biological processes in C. elegans is greatly facilitated by the
fact that the development of this organism occurs in an essentially
invariant manner. The availability of the complete embryonic and
postembryonic somatic cell lineage of C. elegans (Sulston and Horvitz
1977; Sulston et al. 1983) allows an analysis of various processes at
single cell resolution.
During the development of a C. elegans hermaphrodite a total of
1090 somatic cells are formed. Exactly 131 out of these 1090 cells are
eliminated again by a process which, at the morphological level, is
reminiscent of the programmed cell-death process observed in higher
organisms: the dying cells round up and shrink, the cytoplasm and
chromatin condense and eventually the cell corpses are engulfed and
phagocytosed by neighboring cells (Robertson and Thomson 1982).
These programmed cell-death events are determined by cell lineage and
occur in a cell-autonomous manner (Sulston and Horvitz 1977; Sulston
et al. 1983). Programmed cell death in the C. elegans soma can therefore
be regarded as a form of terminal differentiation or as a cell fate. Having
the knowledge of which cells undergo programmed cell death in C.
elegans and when and where this happens, allows a systematic analysis
of the cell-death process at the genetic level in this organism.
3.3 A Genetic Pathway Underlies the Process
of Programmed Cell Death
U sing a genetic approach, mutations have been isolated that block most
if not all somatic programmed cell-death events in C. elegans (reviewed
by Ellis et al. 1991 b; Metzstein et al. 1998). Animals carrying these
mutations have up to 131 extra somatic cells but otherwise develop into
healthy, fertile adults. The identification of cell-death-defective or ced
mutants in C. elegans demonstrated for the first time that the process of
programmed cell death has a genetic basis and that it is the result of the
action of a set of specific genes.
The genetically identified mutations define three genes, ced-3, ced-4,
and ced-9. Loss-of-function mutations in ced-3 or ced-4 block pro-