Genetics of Apoptosis

10.

Apoptosis in Drosophila

Kristin White

1.

Introduction

Genetically tractable model systems have proven invaluable in identifying molecules
important for apoptosis, and for understanding how these molecules interact to
regulate apoptosis during development, and in response to stress. Two widely used
models, the nematode C. elegans and the fruit fly Drosophila melanogaster, demonstrate
distinct advantages for these studies. Genetic screens in C. elegans identified the ced-3
caspase as an essential effector of apoptosis, and the ced-4/Apaf-l adapter proteins
and the ced-9 and egl-1 bcl-2 family members as critical regulators of caspase
activation (reviewed in Chapter 9). Work in a second genetic system, Drosophila, has
uncovered a different caspase regulatory mechanism. As we describe below,
developmental cell death in flies is regulated largely by the anti-apoptotic IAP
proteins, and the proapoptotic Reaper (Rpr), Grim, and Hid proteins. The
identification of different pathways in these two systems probably reflects differences
in the relative importance of these two regulatory systems in worm and fly apoptosis,
as well as distinct biases of the screens used to uncover these pathways. These findings
also highlight the advantages of looking at the same pathways in multiple model
systems.

2.

Genetic screens uncover genes important in developmental

apoptosis

Early studies on developmental cell death in flies revealed that a significant number
of cells die during development, and that the death of these cells resembles apoptosis
as described in mammalian cells, both ultrastructurally and biochemically (Abrams
et al., 1993). A simple assay for apoptosis was developed that facilitated the
examination of cell death in Drosophila embryos. This assay was based on the finding
that acridine orange specifically stained apoptotic cells in living embryos. This allowed
the overall pattern of apoptosis to be rapidly assessed in large numbers of embryos.