NEURITES CAN REMAIN VIABLE AFTER DESTRUCTION OF THE NEURONAL SOMA BY PROGRAMMED CELL-DEATH (APOPTOSIS)

During the development of the nervous system extensive programmed neur onal death occurs that is regulated by neurotrophic factors. Invariabl y, degeneration and death of the neuronal soma as a result of trophic factor deprivation is accompanied by concurrent degeneration of the ne urites. By examining the degeneration of sympathetic neurons after dep rivation of their physiological trophic factor nerve growth factor, we show that the ''slow Wallerian degeneration'' allele (Wld(s)) express ed by homozygous mutant C57BL/Ola mice alters the normal time course o f programmed neuronal death by selectively and dramatically delaying t he onset of neurite disintegration. In contrast, degenerative events a ffecting the neuronal soma are not altered: Atrophy of the soma, apopt otic disintegration of the nucleus, commitment to die, and loss of via bility occur normally. The enucleate neurites remaining after death of the soma have an intact plasma membrane, are metabolically active, an d require an active metabolism for physical integrity. We suggest that the degeneration of neurites during developmentally occuring neuronal death is controlled by events confined to the neurites and occurs aut onomously from the neuronal soma. Furthermore, programmed neuronal dea th of the soma proceeds independent from any influence exerted by dege nerating neurites. (C) 1994 Academic Press, Inc.