Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3

Elife. 2015 Jun 15;4:e05061. doi: 10.7554/eLife.05061.

Abstract

Development and function of highly polarized cells such as neurons depend on microtubule-associated intracellular transport, but little is known about contributions of specific molecular motors to the establishment of synaptic connections. In this study, we investigated the function of the Kinesin I heavy chain Kif5aa during retinotectal circuit formation in zebrafish. Targeted disruption of Kif5aa does not affect retinal ganglion cell differentiation, and retinal axons reach their topographically correct targets in the tectum, albeit with a delay. In vivo dynamic imaging showed that anterograde transport of mitochondria is impaired, as is synaptic transmission. Strikingly, disruption of presynaptic activity elicits upregulation of Neurotrophin-3 (Ntf3) in postsynaptic tectal cells. This in turn promotes exuberant branching of retinal axons by signaling through the TrkC receptor (Ntrk3). Thus, our study has uncovered an activity-dependent, retrograde signaling pathway that homeostatically controls axonal branching.

Keywords: axonal development; neuroscience; neurotrophic signaling; visual system; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Biological Transport / physiology
  • Blotting, Western
  • Cell Polarity / physiology*
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA Primers / genetics
  • Genotype
  • Immunohistochemistry
  • In Situ Hybridization
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism
  • Neurogenesis / physiology*
  • Neurotrophin 3 / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Time-Lapse Imaging
  • Zebrafish / embryology*
  • Zebrafish Proteins / metabolism*

Substances

  • DNA Primers
  • Neurotrophin 3
  • Zebrafish Proteins
  • Kif5aa protein, zebrafish
  • Kinesin

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.