WIDESPREAD ELIMINATION OF NATURALLY-OCCURRING NEURONAL DEATH IN BAX-DEFICIENT MICE

The proapoptotic molecule BAX is required for death of sympathetic and motor neurons in the setting of trophic factor deprivation, Furthermo re, adult Bax-/- mice have more motor neurons than do their wild-type counterparts. these findings raise the possibility that BAX regulates naturally occurring cell death during development in many neuronal pop ulations, To test this idea, we assessed apoptosis using TUNEL labelin g in several well-studied neural systems during embryonic and early po stnatal development in Bax-/- mice. Remarkably, naturally occurring ce ll death is virtually eliminated between embryonic day 11.5 (E11.5) an d postnatal day 1 (PN1) in most peripheral ganglia, in motor pools in the spinal cord. and in the trigeminal brainstem nuclear complex. Addi tionally, reduction, although not elimination, of cell death was noted throughout the developing cerebellum, in some layers of the retina, a nd in the hippocampus. Saving of cells was verified by axon counts of dorsal and ventral roots, as well as facial and optic nerves that reve aled 24-35% increases in axon number, Interestingly, many of the super numerary axons had very small cross-sectional areas, suggesting that t he associated neurons are not normal. We conclude that BAX is a critic al mediator of naturally occurring death of peripheral and CNS neurons during embryonic life. However, rescue from naturally occurring cell death does not imply that the neurons will develop normal functional c apabilities.