To understand better the cellular basis of late-onset neuronal degener
ation, we have examined the brain of the drop-dead mutant of Drosophil
a. This mutant carries an X-chromosomal recessive mutation that causes
severe behavioral defects and brain degeneration, manifested a few da
ys after emergence of the adult. Analysis of genetically mosaic flies
has indicated that the focus of the drop-dead mutant phenotype is in t
he brain and that the gene product is non-cell autonomous. We examined
the adult drop-dead mutant brain prior to onset of symptoms and found
that many glial cells have stunted processes, whereas neuronal morpho
logy is essentially normal. Adult mutant glial cells resemble immature
glia found at an earlier stage of normal brain development. These obs
ervations suggest that defective glia in the drop-dead brain may disru
pt adult nervous system function, contributing to progressive brain de
generation and death. The normal drop-dead gene product may prevent br
ain degeneration by providing a necessary glial function.