Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding

doi:10.1083/jcb.200303168

Published 2 September 2003. doi:10.1083/jcb.200303168

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© The Rockefeller University Press, 0021-9525/2003/9/919 $5.00
The Journal of Cell Biology, Volume 162, Number 5, 919-932

Article

Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding

Michelle L. McWhorter¹^,2, Umrao R. Monani³, Arthur H.M. Burghes²^,3^,4^,5 and Christine E. Beattie¹^,2^,6

¹ Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
² Molecular, Cellular, and Developmental Biology Program
³ Department of Neurology, The Ohio State University, Columbus, OH 43210
⁴ Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210
⁵ Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210
⁶ Department 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: beattie.24{at}osu.edu

Spinal muscular atrophy (SMA) is an autosomal recessive disordercharacterized by a loss of ${alpha}$ motoneurons in the spinal cord.SMA is caused by low levels of the ubiquitously expressed survivalmotor neuron (Smn) protein. As it is unclear how low levelsof Smn specifically affect motoneurons, we have modeled SMAin zebrafish, a vertebrate model organism with well-characterizedmotoneuron development. Using antisense morpholinos to reduceSmn levels throughout the entire embryo, we found motor axon–specificpathfinding defects. Reduction of Smn in individual motoneuronsrevealed that smn is acting cell autonomously. These resultsshow for the first time, in vivo, that Smn functions in motoraxon development and suggest that these early developmentaldefects may lead to subsequent motoneuron loss.

Key Words: SMA; SMN; motoneurons; zebrafish; morpholino

The online version of this article includes supplemental material.

Abbreviations used in this paper: AChR, acetylcholine receptor;CaP, caudal primary; MO, morpholino oligonucleotide; SMA, spinalmuscular atrophy; SMN, survival motor neuron; VeLD, ventrallongitudinal descending.

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