Genetics of Programmed Cell Death

To live or die is a fundamental question for all organisms. It is also a critical issue at the level of individual cells of an organism. Programmed cell death or apoptosisapoptosisdefined is required as a normal process for proper development or occurs in response to various harmful stimuli. Thus, genetic regulation of programmed cell death is essential in diverse biological processes and diseases, including cancer. This chapter focuses on genetic studies of cell death in C. eleganscell death and Drosophilacell death as ideal model organisms. Identified lineages of dying cells in developing C. elegans provide an excellent system for the genetic dissection of cell death mechanisms. We will discuss the first genetic screen for cell death mutants in C. elegans. Discoveries of proapoptotic cell death (ced) genes such as ced-3 and ced-4 are described. Bcl-2-like protein encoded by ced-9 antagonizes proapoptotic gene functions. Functional relationships of these genes in the cell death pathway will be discussed. Next, we will examine a different genetic approach for finding cell death genes in Drosophila. A systematic screen for chromosomal deficiencies that abolish programmed cell death in embryos will be discussed. Subsequent studies on cell death genes, such as reaper, hid, and grim, were crucial for understanding this system’s apoptosis mechanism. Lastly, we will compare apoptotic cell death mechanisms in invertebrate and mammalian models.