The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis

Inactivation of the gene encoding the POU domain transcription factor BRN-3 A results in the absence of specific neurons in knockout mice. Here we demo nstrate for the first time a direct effect of BRN-3A on the survival of neu ronal cells. Specifically, overexpression of BRN-3A in cultured trigeminal ganglion or dorsal root ganglion sensory neurons enhanced their survival fo llowing the withdrawal of nerve growth factor. Moreover, reduction of BRN-3 A levels impaired the survival of these neurons, The survival of sympatheti c neurons was not affected by either approach. Similarly, overexpression of BRN-3A activated the endogenous Bcl-2 gene in trigeminal neurons, but not in sympathetic neurons. The protective effect of BRN-3A on trigeminal neuro n survival following nerve growth factor withdrawal significantly increased during embryonic development. In contrast, overexpression of the related f actor BRN-3B enhanced survival of trigeminal neurons only at an early stage of embryonic development. Thus, BRN-3A (and in some circumstances, BRN-3B) can promote the survival of nerve growth factor-dependent sensory but not sympathetic neurons, allowing it to play a direct role in the survival of s ome (but not all) neuronal populations in the developing and adult nervous systems.