title: Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development.
abstract: Childhood spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by absent or deficient full-length survival motor neuron (SMN) protein. Clinical studies and animal models suggest that SMA is a developmental defect in neuromuscular interaction; however, the role of SMN in this process remains unclear. In the present study, we have determined the subcellular localization of SMN during retinoic-acid-induced neuronal differentiation of mouse embryonal teratocarcinoma P19 cells as well as in skeletal muscle during the critical period of neuromuscular maturation. We demonstrate, for the first time, SMN accumulation in growth-cone- and filopodia-like structures in both neuronal- and glial-like cells, identifying SMN as a new growth cone marker. Indeed, SMN was present at the leading edge of neurite outgrowths, suggesting that SMN may play a role in this process. In addition, SMN was detected as small dot-like particles within the cytoplasm of skeletal muscle during the first 2 weeks after birth, but their number peaked by P6. Intense SMN staining in neuromuscular junctions was observed throughout the entire postnatal period examined. Taken together, these results suggest that SMN may indeed fulfill neuronal- and muscle-specific functions, providing a more plausible mechanism explaining motor neuron degeneration and associated denervation atrophy of skeletal muscles in SMA. The primary SMA pathology most likely initiates in the peripheral axon--the result of deficient neurite outgrowth and/or neuromuscular maturation.
authors.affiliation: Centre de Recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada H3T 1C5.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Louise R
authors.initials: LR
authors.lastname: Simard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D019070:Cell Lineage; D017362:Cyclic AMP Response Element-Binding Protein; D015536:Down-Regulation; D020439:Growth Cones / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D018243:Teratocarcinoma / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins