PUBLICATION
Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding
- Authors
- McWhorter, M.L., Monani, U.R., Burghes, A.H., and Beattie, C.E.
- ID
- ZDB-PUB-030908-5
- Date
- 2003
- Source
- The Journal of cell biology 162(5): 919-932 (Journal)
- Registered Authors
- Beattie, Christine
- Keywords
- none
- MeSH Terms
-
- Animals
- Axons/metabolism*
- Cell Death/physiology
- Cell Movement/physiology*
- Cyclic AMP Response Element-Binding Protein
- Humans
- In Situ Hybridization
- Motor Neurons/cytology
- Motor Neurons/metabolism*
- Muscular Atrophy, Spinal/metabolism
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Neuromuscular Junction
- Oligonucleotides, Antisense/metabolism
- RNA-Binding Proteins
- Receptors, Cholinergic/metabolism
- SMN Complex Proteins
- Survival of Motor Neuron 1 Protein
- Zebrafish/anatomy & histology
- Zebrafish/embryology*
- Zebrafish/physiology
- PubMed
- 12952942 Full text @ J. Cell Biol.
Citation
McWhorter, M.L., Monani, U.R., Burghes, A.H., and Beattie, C.E. (2003) Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. The Journal of cell biology. 162(5):919-932.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping