Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish.
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.
Welsh
Lillian
L
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Tanguay
Robert L
RL
Svoboda
Kurt R
KR
D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects* / Q000648:ultrastructure; D007120:Immunochemistry; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000196:embryology / Q000294:innervation / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017354:Point Mutation; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D018709:Statistics, Nonparametric; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D029961:Zebrafish Proteins; D009538:Nicotine