36
B. Conradt
one hand and the programmed death of cells on the other hand, determine the overall rate of cell proliferation. The proper regulation of these
two physiological processes is therefore a crucial aspect of development
and of tissue homeostasis (reviewed by Edgar and Lehner 1996; Sherr
1996; Jacobson et al. 1997; Rinkenberger and Korsmeyer 1997). While
the importance of the process of cell division has long been recognized,
the role and extent of programmed cell death, or apoptosis, has only
been realized within the last decades (Gliicksmann 1950; Kerr et al.
1972). Massive programmed cell death occurs, for instance, during the
development of the nervous system and in the immune system: more
than 50% of all neurons and oligodendrocytes formed in the peripheral
and central vertebrate nervous system undergo programmed cell death
during neurogenesis (reviewed by Oppenheimer 1991; Pettmann and
Henderson 1998) and more than 95% of all thymocytes generated die by
programmed cell death during maturation (reviewed by Duvall and
Wyllie 1986; Nagata 1997). The importance of the programmed celldeath process is underlined by the fact that when deregulated in humans,
programmed cell death can cause disease (reviewed by Thompson
1995). A block in programmed cell death can lead to cancer or autoimmune diseases and increased programmed cell death appears to be
involved in a number of neurodegenerative diseases.
Studies of the nematode Caenorhabditis elegans have contributed
greatly to our current knowledge of programmed cell death. In this
chapter, I will review genetic analyses in C. elegans that led to the
identification of the central pathway required for programmed cell death
in this organism. I will then summarize data which have revealed some
of the molecular mechanisms that underlie this pathway. Finally, I will
discuss recent findings which have implications for how the cell-death
pathway might be initiated and regulated during the development and
throughout the adult life of C. elegans.
3.2 C. elegans Is Amenable to Genetic Analyses
of the Programmed Cell-Death Process
Due to its short life cycle, its small genome, and the ease with which it
can be cultivated in large numbers, C. elegans has proven to be an
excellent organism for genetic analyses (Wood et al. 1988; Riddle et al.
B. Conradt
one hand and the programmed death of cells on the other hand, determine the overall rate of cell proliferation. The proper regulation of these
two physiological processes is therefore a crucial aspect of development
and of tissue homeostasis (reviewed by Edgar and Lehner 1996; Sherr
1996; Jacobson et al. 1997; Rinkenberger and Korsmeyer 1997). While
the importance of the process of cell division has long been recognized,
the role and extent of programmed cell death, or apoptosis, has only
been realized within the last decades (Gliicksmann 1950; Kerr et al.
1972). Massive programmed cell death occurs, for instance, during the
development of the nervous system and in the immune system: more
than 50% of all neurons and oligodendrocytes formed in the peripheral
and central vertebrate nervous system undergo programmed cell death
during neurogenesis (reviewed by Oppenheimer 1991; Pettmann and
Henderson 1998) and more than 95% of all thymocytes generated die by
programmed cell death during maturation (reviewed by Duvall and
Wyllie 1986; Nagata 1997). The importance of the programmed celldeath process is underlined by the fact that when deregulated in humans,
programmed cell death can cause disease (reviewed by Thompson
1995). A block in programmed cell death can lead to cancer or autoimmune diseases and increased programmed cell death appears to be
involved in a number of neurodegenerative diseases.
Studies of the nematode Caenorhabditis elegans have contributed
greatly to our current knowledge of programmed cell death. In this
chapter, I will review genetic analyses in C. elegans that led to the
identification of the central pathway required for programmed cell death
in this organism. I will then summarize data which have revealed some
of the molecular mechanisms that underlie this pathway. Finally, I will
discuss recent findings which have implications for how the cell-death
pathway might be initiated and regulated during the development and
throughout the adult life of C. elegans.
3.2 C. elegans Is Amenable to Genetic Analyses
of the Programmed Cell-Death Process
Due to its short life cycle, its small genome, and the ease with which it
can be cultivated in large numbers, C. elegans has proven to be an
excellent organism for genetic analyses (Wood et al. 1988; Riddle et al.