Connectomics of the zebrafish's lateral-line neuromast reveals wiring and miswiring in a simple microcircuit

Elife. 2018 Jun 12:7:e33988. doi: 10.7554/eLife.33988.

Abstract

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 used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated 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.

Keywords: auditory system; electron microscopy; hair cell; neuroscience; ribbon synapse; vestibular system; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / cytology
  • Afferent Pathways / physiology*
  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Cell Polarity
  • Efferent Pathways / cytology
  • Efferent Pathways / physiology*
  • Embryo, Nonmammalian
  • Ganglia / cytology
  • Ganglia / physiology
  • Gene Expression
  • Hair Cells, Auditory / physiology*
  • Hair Cells, Auditory / ultrastructure
  • Larva / anatomy & histology
  • Larva / physiology
  • Lateral Line System / cytology
  • Lateral Line System / innervation
  • Lateral Line System / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Nerve Fibers / physiology
  • Nerve Fibers / ultrastructure
  • Neural Pathways / physiology*
  • Neural Pathways / ultrastructure
  • Optical Imaging
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Zebrafish / anatomy & histology
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Membrane Proteins
  • Receptors, Notch
  • Zebrafish Proteins
  • vangl2 protein, zebrafish