Xenopus Bcl-X-L selectively protects Rohon-Beard neurons from metamorphic degeneration

Amphibian metamorphosis involves extensive, but selective, neuronal death a nd turnover, thus sharing many features with mammalian postnatal developmen t. The antiapoptotic protein Bcl-X-L plays an important role in postnatal m ammalian neuronal survival. It is therefore of interest that accumulation o f the mRNA encoding the Xenopus Bcl-XL homologue, termed xR11, increases ab ruptly in the nervous system, but not in other tissues, during metamorphosi s in Xenopus tadpoles. This observation raises the intriguing possibility t hat xR11 selectively regulates neuronal survival during postembryonic devel opment. To investigate this hypothesis, we overexpressed xR11 in vivo as a green fluorescent protein (GFP)-xR11 fusion protein by using somatic and ge rminal transgenesis, somatic gene transfer showed that the fusion protein w as effective in counteracting, in a dose-dependent manner, the proapoptotic effects of coexpressed Bar. When GFP-xR11 was expressed from the neuronal P-tubulin promoter by germinal transgenesis we observed neuronal specific e xpression that was maintained throughout metamorphosis and beyond, into juv enile and adult stages. Confocal microscopy showed GFP-xR11 to be exclusive ly localized in the mitochondria, Our findings show that CFP-xR11 significa ntly prolonged Rohon-Beard neuron survival up to the climax of metamorphosi s, even in the regressing tadpole tail, whereas in controls these neurons d isappeared in early metamorphosis. However, CFP-xR11 expression did not mod ify the fate of spinal cord motoneurons. The selective protection of Rohon- Beard neurons reveals cell-specific apoptotic pathways and offers approache s to further analyze programmed neuronal turnover during postembryonic deve lopment.