SCHWANN-CELL APOPTOSIS DURING NORMAL DEVELOPMENT AND AFTER AXONAL DEGENERATION INDUCED BY NEUROTOXINS IN THE CHICK-EMBRYO

In the present work, we show that chick embryo Schwann cells die by ap optosis both during normal development and after axonal degeneration i nduced by neurotoxin treatment. Schwann cell apoptosis during developm ent takes place during a period roughly coincidental with normally occ urring motoneuron death. Administration of NMDA to chick embryos on em bryonic day 7 induces extensive excitotoxic motoneuronal damage in the spinal cord without any apparent effects on neurons in the dorsal roo t ganglia (DRG). The death of Schwann cells in ventral nerve roots aft er NMDA treatment causes degenerative changes that display ultrastruct ural features of apoptosis and exhibit in situ detectable DNA fragment ation. By contrast, NMDA treatment does not increase the death of Schw ann cells in dorsal nerve roots. In situ detection of DNA fragmentatio n in combination with the avian Schwann cell marker 1E8 antibody demon strates that dying cells in ventral nerve roots are in the Schwann cel l lineage. Administration of cycloheximide does not prevent the toxic effects of NMDA on motoneurons, but dramatically reduces the number of pyknotic Schwann cells and DNA fragmentation profiles in the ventral nerve roots. In ovo administration of various tissue extracts (muscle, brain, and spinal cord) from the chick embryo or of the motoneuron co nditioned medium fails to prevent Schwann cell apoptosis in NMDA-treat ed embryos. Intramuscular administration of the snake toxin beta-bunga rotoxin produces a massive death of both lateral motor column motoneur ons and DRG neurons, resulting in a substantial increase in the number of pyknotic Schwann cells in both ventral and dorsal nerve roots. It is concluded that during development, axonal-derived trophic signals a re involved in the regulation of Schwann cell survival in peripheral n erves.