title: SMN, the product of the spinal muscular atrophy-determining gene, is expressed widely but selectively in the developing human forebrain.
abstract: The expression pattern of the survival motor neuron (SMN) protein has been investigated immunohistochemically in the human fetal forebrain from 14 to 38 weeks of gestation. Mutations in the SMN gene cause spinal muscular atrophy (SMA), an autosomal recessive disease characterized by degeneration of lower motor neurons in the spinal cord leading to progressive muscle wasting. SMN is a multifunctional protein and has been implicated in diverse cytoplasmic and nuclear processes. The monoclonal murine SMN antibody used in this study recognized a major band at approximately 34 kDa. In spinal cord anterior horn motor neurons at 13 weeks of gestation, the soma, proximal neurites, and nucleus were immunostained. In the nucleus, SMN immunolabeling was observed at the nuclear membrane, at the nucleolus, and at dot-like structures in the nucleoplasm likely to be coiled bodies and gems. In the fetal forebrain, SMN was immunodetected as early as 14 weeks of gestation. From 14 to 24 weeks of gestation, intense immunostaining was observed in the basal nucleus of Meynert, a major source of cholinergic afferents to the cortex. Less intensely labeled cells at lower packing density were also observed in the thalamus, reticular and perireticular nucleus, globus pallidus, hippocampus, amygdala, and enthorinal cortex. Immunolabeled cells were still detectable at 38 gestational weeks, the latest time point investigated. These findings provide an anatomical basis for future investigations of SMN functions during brain development and for the neuropathological characterization of severe SMA cases.
authors.affiliation: MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford OX1 3QX, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Briese
authors.forename: Dagmar-Ulrike
authors.initials: DU
authors.lastname: Richter
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
authors.forename: Norbert
authors.initials: N
authors.lastname: Ulfig
mesh_terms: D000870:Anterior Horn Cells / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D020532:Basal Nucleus of Meynert / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012016:Reference Values; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins