title: Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding.
abstract: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of alpha motoneurons in the spinal cord. SMA is caused by low levels of the ubiquitously expressed survival motor neuron (Smn) protein. As it is unclear how low levels of Smn specifically affect motoneurons, we have modeled SMA in zebrafish, a vertebrate model organism with well-characterized motoneuron development. Using antisense morpholinos to reduce Smn levels throughout the entire embryo, we found motor axon-specific pathfinding defects. Reduction of Smn in individual motoneurons revealed that smn is acting cell autonomously. These results show for the first time, in vivo, that Smn functions in motor axon development and suggest that these early developmental defects may lead to subsequent motoneuron loss.
authors.affiliation: Center for Molecular Neurobiology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: McWhorter
authors.forename: Umrao R
authors.initials: UR
authors.lastname: Monani
authors.forename: Arthur H M
authors.initials: AH
authors.lastname: Burghes
authors.forename: Christine E
authors.initials: CE
authors.lastname: Beattie
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein; D006801:Humans; D017403:In Situ Hybridization; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D016601:RNA-Binding Proteins; D011950:Receptors, Cholinergic / Q000378:metabolism; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D016601:RNA-Binding Proteins; D011950:Receptors, Cholinergic; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; C526474:smn1 protein, zebrafish