Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system.

摘要

Despite recent data on the cellular function of the survival motor neuron (SMN) gene, the spinal muscular atrophy (SMA) disease gene, the role of the SMN protein in motor neurons and hence in the pathogenesis of SMA is still unclear. The spatial and temporal expression of SMN in neurons, particularly during development, could help in verifying the hypotheses on the SMN protein functions so far proposed. We have therefore investigated the expression and subcellular localization of the SMN protein in the human central nervous system (CNS) during ontogenesis with immunocytochemical, confocal immunofluorescence, and Western blot experiments using a panel of anti-SMN antibodies recognizing the full-length SMN protein. The experiments not only revealed the early SMN expression in all neurons, but also demonstrated the progressive shift in SMN subcellular localization from mainly nuclear to cytoplasmic and then to axons during CNS maturation. This finding was present in selected neuronal cell populations and it was particularly conspicuous in motor neurons. Our data support the idea of a specific role for SMN in axons, which becomes predominant in the ontogenetic period encompassing axonogenesis and axonal sprouting. In addition, the asymmetric SMN staining demonstrated in the germinative neuroepithelium suggests a possible role for SMN in neuronal migration and/or differentiation.