Muscle Contractions Guide Rohon–Beard Peripheral Sensory Axons

Abstract

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.

Activation of α2A‐containing nicotinic acetylcholine receptors mediates nicotine‐induced motor output in embryonic zebrafish

“…We then examined aspects of RB neuron anatomy and development, focusing on RB neuron peripheral processes and RB neuron migration. RB cells extend peripheral processes into the skin along a stereotypical ventral–lateral trajectory and these processes can be easily visualized within the skin using aat immunoreactivity (Svoboda et al ., ; Paulus et al ., ). By 48 hpf, the tubulin distribution within the peripheral processes of RB neurons is typically fragmented, and this fragmentation serves as a marker of RB neurons that have entered into programmed cell death (Svoboda et al ., ).…”

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

“…For example, Weiss (1941) described the process of stretch growth of axons, and recent experiments have documented the extensive influence of stretch forces on axon growth rates (Pfister et al, 2004). Likewise, muscle contractions are crucial for the axonal guidance of Rohon-Beard cells in developing zebrafish (Paulus et al, 2009). Although the extensive influence of extrinsic mechanical forces on neuronal development is well documented, the cellular mechanisms by which these forces are detected and harnessed are poorly understood.…”

The mechanical control of nervous system development

“…Accordingly, when neurons are cultured on a flexible substrate, neurite extension significantly increases with increasing substrate stretching, and neurites preferentially align along the stretch direction (Chang et al, 2013). Similarly, muscle contractions in zebrafish generate mechanical forces that are required for proper pathfinding of sensory axons growing between the muscle and the skin of the fish (Paulus et al, 2009). Another example of the involvement of tension in axonal growth and guidance in vivo is exhibited by migrating primordium cells in the developing zebrafish, which not only tow axons of sensory neurons but also guide their pathfinding in this way (Gilmour et al, 2004).…”