title: Embryonic motor axon development in the severe SMA mouse.
abstract: Spinal muscular atrophy (SMA) is caused by reduced levels of survival motor neuron (SMN) protein. Previously, cultured SMA motor neurons showed reduced growth cone size and axonal length. Furthermore, reduction of SMN in zebrafish resulted in truncation followed by branching of motor neuron axons. In this study, motor neurons labeled with green fluorescent protein (GFP) were examined in SMA mice from embryonic day 10.5 to postnatal day 2. SMA motor axons showed no defect in axonal formation or outgrowth at any stage of development. However, a significant increase in synapses lacking motor axon input was detected in embryonic SMA mice. Therefore, one of the earliest detectable morphological defects in the SMA mice is the loss of synapse occupation by motor axons. This indicates that in severe SMA mice there are no defects in motor axon formation however, we find evidence of denervation in embryogenesis.
authors.affiliation: Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: McGovern
authors.forename: Tatiana O
authors.initials: TO
authors.lastname: Gavrilina
authors.forename: Christine E
authors.initials: CE
authors.lastname: Beattie
authors.forename: Arthur H M
authors.initials: AH
authors.lastname: Burghes
mesh_terms: D000818:Animals; D001369:Axons / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000737:chemistry / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009134:Muscular Atrophy, Spinal / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000196:embryology / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; C526474:smn1 protein, zebrafish