Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of α 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.
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1 September 2003
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September 02 2003
Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding
Michelle L. McWhorter,
Michelle L. McWhorter
1Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
2Molecular, Cellular, and Developmental Biology Program
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Umrao R. Monani,
Umrao R. Monani
3Department of Neurology, The Ohio State University, Columbus, OH 43210
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Arthur H.M. Burghes,
Arthur H.M. Burghes
2Molecular, Cellular, and Developmental Biology Program
3Department of Neurology, The Ohio State University, Columbus, OH 43210
4Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210
5Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210
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Christine E. Beattie
Christine E. Beattie
1Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
2Molecular, Cellular, and Developmental Biology Program
6Department of Neuroscience, The Ohio State University, Columbus, OH 43210
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Michelle L. McWhorter
1Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
2Molecular, Cellular, and Developmental Biology Program
Umrao R. Monani
3Department of Neurology, The Ohio State University, Columbus, OH 43210
Arthur H.M. Burghes
2Molecular, Cellular, and Developmental Biology Program
3Department of Neurology, The Ohio State University, Columbus, OH 43210
4Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210
5Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210
Christine E. Beattie
1Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
2Molecular, Cellular, and Developmental Biology Program
6Department of Neuroscience, The Ohio State University, Columbus, OH 43210
Address correspondence to Christine E. Beattie, Center for Molecular Neurobiology, The Ohio State University, 115 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210. Tel.: (614) 292-5113. Fax: (614) 292-5379. email: [email protected]
The online version of this article includes supplemental material.
Abbreviations used in this paper: AChR, acetylcholine receptor; CaP, caudal primary; MO, morpholino oligonucleotide; SMA, spinal muscular atrophy; SMN, survival motor neuron; VeLD, ventral longitudinal descending.
Received:
March 26 2003
Accepted:
July 14 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 162 (5): 919–932.
Article history
Received:
March 26 2003
Accepted:
July 14 2003
Citation
Michelle L. McWhorter, Umrao R. Monani, Arthur H.M. Burghes, Christine E. Beattie; Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding . J Cell Biol 1 September 2003; 162 (5): 919–932. doi: https://doi.org/10.1083/jcb.200303168
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