Defective glia in the Drosophila brain degeneration mutant drop-dead.

To understand better the cellular basis of late-onset neuronal degeneration, we have examined the brain of the drop-dead mutant of Drosophila. This mutant carries an X-chromosomal recessive mutation that causes severe behavioral defects and brain degeneration, manifested a few days after emergence of the adult. Analysis of genetically mosaic flies has indicated that the focus of the drop-dead mutant phenotype is in the 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 morphology is essentially normal. Adult mutant glial cells resemble immature glia found at an earlier stage of normal brain development. These observations suggest that defective glia in the drop-dead brain may disrupt adult nervous system function, contributing to progressive brain degeneration and death. The normal drop-dead gene product may prevent brain degeneration by providing a necessary glial function.