Muscle contractions guide rohon-beard peripheral sensory axons.
Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth; however, whether mechanical force contributes to axon guidance in vivo is unknown. We investigated the role of muscle contractions in the guidance of zebrafish peripheral Rohon-Beard (RB) sensory axons in vivo. We analyzed several mutants that affect muscle contraction through different molecular pathways, including a new mutant allele of the titin a (pik) gene, mutants that affect the hedgehog signaling pathway, and a nicotinic acetylcholine receptor mutant. We found RB axon defects in these mutants, the severity of which appeared to correlate with the extent of muscle contraction loss. These axons extend between the muscle and skin and normally have ventral trajectories and repel each other on contact. RB peripheral axons in muscle mutants extend longitudinally instead of ventrally, and the axons fail to repel one another on contact. In addition, we showed that limiting muscle movements by embedding embryos in agarose caused similar defects in peripheral RB axon guidance. This work suggests that the mechanical forces generated by muscle contractions are necessary for proper sensory axon pathfinding in vivo.
Departments of Zoology and Anatomy and Cell and Molecular Biology Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
Jeremiah D
JD
Paulus
Gregory B
GB
Willer
Jason R
JR
Willer
Ronald G
RG
Gregg
Mary C
MC
Halloran
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D064211:Connectin; D004625:Embryo, Nonmammalian / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010525:Peripheral Nerves / Q000166:cytology*; D011494:Protein Kinases / Q000235:genetics; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D064211:Connectin; D053823:Hedgehog Proteins; D009124:Muscle Proteins; D003473:Neuromuscular Nondepolarizing Agents; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; D019765:Chondroitin ABC Lyase; D014403:Tubocurarine