TitleUncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish.
Publication TypeJournal Article
Year of Publication2009
AuthorsWelsh, L, Tanguay, RL, Svoboda, KR
JournalToxicol Appl Pharmacol
Volume237
Issue1
Pagination29-40
Date Published2009 May 15
ISSN1096-0333
KeywordsAnimals, Animals, Genetically Modified, Cell Movement, Embryo, Nonmammalian, Growth Cones, Immunochemistry, Motor Neurons, Muscle Development, Muscle, Skeletal, Nicotine, Nicotinic Agonists, Point Mutation, Receptors, Nicotinic, Spinal Cord, Statistics, Nonparametric, Zebrafish, Zebrafish Proteins
Abstract

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.

DOI10.1016/j.taap.2008.06.025
Alternate JournalToxicol. Appl. Pharmacol.
PubMed ID18694773
PubMed Central IDPMC2896658
Grant ListES016513 / ES / NIEHS NIH HHS / United States
R01 ES016513 / ES / NIEHS NIH HHS / United States
P30-ES00210 / ES / NIEHS NIH HHS / United States
R01 ES016513-02 / ES / NIEHS NIH HHS / United States
R01 ES016513-01A2 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States