BCL-2 IS REQUIRED FOR CRANIAL SENSORY NEURON SURVIVAL AT DEFINED STAGES OF EMBRYONIC-DEVELOPMENT

To ascertain the role of endogenous Bcl-2 in maintaining the survival of developing neurons and modulating their responses to neurotrophins, we compared the in vitro and in vivo survival of cranial sensory neur ons of wild-type and bcl-2 null mouse embryos, At the peak of naturall y occurring neuronal death in the trigeminal ganglion at E14, trigemin al neurons from bcl-2(-/-) embryos initially survived in culture in re sponse to NGF but were not sustained as well as neurons from wild-type embryos, At the end of the period of naturally occurring neuronal dea th at E18, Bcl-2-deficient trigeminal neurons survived with NGF as wel l as wild-type neurons, At E14 in vivo, the number of trigeminal neuro ns undergoing apoptosis was significantly greater in bcl-2(-/-) embryo s, and there were significantly fewer neurons in the trigeminal gangli a of bcl-2(-/-) embryos at E16 and E18, Similar age-related changes in the responses of nodose ganglion neurons to BDNF were observed in cul tures established from bcl-2(-/-) and wild-type embryos between E14 an d E18, These results suggest that endogenous Bcl-2 is required for the sustained survival response of a subset of cranial sensory neurons to neurotrophins at particular stages of embryonic development and show that its absence leads to reduced numbers of these neurons in vivo.