Differences in Bcl-2-and Bax-independent function in regulating apoptosis in sensory neuron populations

Bcl-2 and Bax are cytoplasmic proteins that have antagonistic actions on ap optosis. To investigate the extent to which these proteins function indepen dently in regulating neuronal apoptosis, we studied the in vivo and in vitr o development of two populations of sensory neurons of mouse embryos that l ack one or both proteins. Absence of Bcl-2 increased neuronal apoptosis and reduced the number of neurons in both the trigeminal and nodose ganglia du ring the period of naturally occurring neuronal death. Absence of Bax reduc ed neuronal apoptosis and increased the number of surviving neurons in thes e ganglia and promoted sustained neuronal survival in neurotrophin-free cul tures. In contrast, the elimination of both Bcl-2 and Bax had different con sequences for these populations of neurons. In nodose ganglia, apoptosis wa s suppressed just as effectively in embryos lacking both proteins as in emb ryos lacking Bax alone, and neurons that lacked both proteins survived just as effectively in neurotrophin-free medium as Bax-deficient neurons. This suggests that for nodose neurons, the suppression of apoptosis by Bcl-2 is entirely dependent on the presence of Bax. In trigeminal ganglia, although neuronal apoptosis was reduced in embryos lacking both proteins compared wi th wild-type embryos, there were significantly more apoptotic neurons and s ignificantly fewer surviving neurons in embryos lacking both proteins compa red with Bax-deficient embryos, and significantly fewer trigeminal neurons from embryos lacking both proteins survived in neurotrophin-free medium com pared with trigeminal neurons that lacked Bax alone. This suggests that for trigeminal neurons, Bcl-2 functions partly independently of Bax in regulat ing survival. Our results therefore suggest that the relative independence of Bcl-2 and Bax in regulating neuronal survival differs from one populatio n of neurons to another.