Connectomics of normal and mutant lateral-line neuromasts
The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We use serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, or comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineates a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity gene vangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.
A detailed reconstruction of a neuromast shows portions of eight mature hair cells (blue and red) and one immature pair (pink and lavender). Their basal surfaces are contacted by nine extensively branched nerve fibers, eight of them afferents and one (black) an efferent. The pink nascent hair cell extends a transient process that apparently attracts innervation.