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Axonal defasciculation is restricted to specific branching points during regeneration of the lateral line nerve in zebrafish

ABSTRACT: Peripheral nerve regeneration requires precise selection of the appropriate targets of innervation, often in an environment that differs from the developmental wiring of the neural circuit. Severed axons of the zebrafish posterior lateral line nerve have the capacity to reinnervate mechanosensory neuromast organs positioned at discrete locations along the fish’s trunk. Nerve regeneration is a balance between fasciculated regrowth of the axonal bundle and defasciculation of individual axons into the epidermis where neuromasts reside. The intrinsic and extrinsic factors that guide pathfinding during regeneration of the posterior lateral line nerve are unknown. Here we show that the gene col18a1a, which codes for the secreted heparan sulfate proteoglycan collagen XVIII, biases axon defasciculation to specific choice points along the fish’s trunk that coincide with circumscribed gaps in the extracellular matrix. We found that col18a1a is expressed by the neuromast and by a subset of Schwann cells that are located at the point of axonal defasciculation. Furthermore, we observed aberrant axon branching at inappropriate locations during nerve regeneration in col18a1a mutants, suggesting an auxiliary role for guiding axon growth cones. We propose a model in which a collagen XVIII-axon guidance cue complex attracts defasciculated arbors across the epidermal basement membrane during posterior lateral line nerve regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE297706 | GEO | 2025/07/23

REPOSITORIES: GEO

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