PgmNr D108: An autonomous requirement of the lysosomal nuclease DNaseII in a caspase-independent primordial germ cell death in the Drosophila embryo.

Authors:
L. Tarayrah; E. Arama


Institutes
The Weizmann Institute of Science, Rehovot, IL.


Keyword: other ( alternative cell death )

Abstract:

Programmed cell death (PCD) is an intracellular genetic program that is activated by all dying metazoan cells. Apoptosis is the most abundant form of PCD and is manifested by the activation of cysteine proteases called caspases. However, activation of caspases does not always lead to apoptosis and emerging evidence suggests the existence caspase-independent alternative cell death (ACD) pathways. Considering that cancer cells have developed ways to evade apoptotic cell death, uncovering the molecular mechanisms underlying ACD pathways has tremendous therapeutic value. However, progress in this field has been slow primarily due to the lack of physiological paradigms of ACD. In this study, we characterize the non-apoptotic cell death of primordial germ cells (PGCs) in the Drosophila embryo. During the early stages of embryo development, germ-line progenitors known as pole cells originate at the posterior pole and must migrate to their somatic partners in order to form the embryonic gonad. Prior studies have demonstrated the involvement of guidance cues that drive PGC migration, while mismigrating germ cells that remain ectopic to the gonad are eliminated. These findings suggest the existence of a mechanism within the embryo that regulates germ cell survival, however little is known about the molecular details governing this elimination mechanism. Our results indicate that PGCs that do no coalesce into a gonad by stage 13 of embryo development undergo caspase-independent cell death that involves the activity of lysosomes. We also find that DNaseII, a lysosomal deoxyribonuclease, is required maternally and cell autonomously in PGCs to drive their elimination providing an excellent physiological system to investigate a caspase-independent cell death pathway in vivo. .