Portal de Periódicos da CAPES

Brn-3a Activates the Expression of Bcl-xL and Promotes Neuronal Survival in Vivo as Well as in Vitro

2001; Elsevier BV; Volume: 17; Issue: 3 Linguagem: Inglês

10.1006/mcne.2000.0927

1095-9327

Martin D. Smith, Lisa Melton, Elizabeth Ensor, Graham Packham, Patrick N. Anderson, Ross A. Kinloch, David S. Latchman,

Bioactive Compounds and Antitumor Agents

The determination of cell fate plays a critical role during the later stages of embryogenesis and the early postnatal period-a time during which approximately half of neurons born during neurogenesis undergo programmed cell death. It has previously been reported that the type IV POU domain transcription factor Brn-3a plays a role in the maturation and survival of sensory neuronal populations. Indeed we have shown that the long form of Brn-3a is capable of activating expression of the antiapoptotic Bcl-2 gene and enhancing neuronal survival in cultures of sensory neurons. In this study, we report the identification of another antiapoptotic family member, Bcl-x(L), as a target gene of Brn-3a in sensory neurons, providing a further mechanism by which Brn-3a determines sensory neuronal fate during development. Bcl-x(L) gene expression is activated by Brn-3a in sensory but not in sympathetic neurons and its expression is reduced by antisense inhibition of Brn-3a expression in sensory neurons. Most importantly, both Bcl-x(L) expression and neuronal survival are enhanced by the overexpression of Brn-3a in dorsal root ganglion in vivo in a model of sciatic nerve injury in the intact animal.