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First published online 10 December 2003
doi: 10.1242/dev.00933
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1 Center for Biosystems Research, University of Maryland Biotechnology
Institute, College Park, Maryland 20742, USA
2 Department of Cell Biology and Molecular Genetics, University of Maryland,
College Park, Maryland 20742, USA
* Author for correspondence (e-mail: baehreck{at}umbi.umd.edu)
Accepted 20 October 2003
Self-digestion of cytoplasmic components is the hallmark of autophagic
programmed cell death. This auto-degradation appears to be distinct from what
occurs in apoptotic cells that are engulfed and digested by phagocytes.
Although much is known about apoptosis, far less is known about the mechanisms
that regulate autophagic cell death. Here we show that autophagic cell death
is regulated by steroid activation of caspases in Drosophila salivary
glands. Salivary glands exhibit some morphological changes that are similar to
apoptotic cells, including fragmentation of the cytoplasm, but do not appear
to use phagocytes in their degradation. Changes in the levels and localization
of filamentous Actin, 
-Tubulin, -Spectrin and nuclear Lamins
precede salivary gland destruction, and coincide with increased levels of
active Caspase 3 and a cleaved form of nuclear Lamin. Mutations in the
steroid-regulated genes ßFTZ-F1, E93, BR-C and E74A
that prevent salivary gland cell death possess altered levels and localization
of filamentous Actin, -Tubulin, -Spectrin, nuclear Lamins and
active Caspase 3. Inhibition of caspases, by expression of either the caspase
inhibitor p35 or a dominant-negative form of the initiator caspase Dronc, is
sufficient to inhibit salivary gland cell death, and prevent changes in
nuclear Lamins and -Tubulin, but not to prevent the reorganization of
filamentous Actin. These studies suggest that aspects of the cytoskeleton may
be required for changes in dying salivary glands. Furthermore, caspases are
not only used during apoptosis, but also function in the regulation of
autophagic cell death.
Key words: Autophagic cell death, Apoptosis, Caspases, Salivary glands, Drosophila
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