ZFIN ID: ZDB-PUB-200610-8
Long-Range Optogenetic Control of Axon Guidance Overcomes Developmental Boundaries and Defects
Harris, J.M., Wang, A.Y., Boulanger-Weill, J., Santoriello, C., Foianini, S., Lichtman, J.W., Zon, L.I., Arlotta, P.
Date: 2020
Source: Developmental Cell   53: 577-588.e7 (Journal)
Registered Authors: Harris, James, Santoriello, Cristina, Zon, Leonard I.
Keywords: axon guidance, axons, embryonic development, nerve regeneration, neuronal outgrowth, neurons, optogenetics, rac GTP-binding proteins, tissue engineering, zebrafish
MeSH Terms:
  • Animals
  • Axon Guidance*
  • Cells, Cultured
  • Motor Neurons/cytology*
  • Motor Neurons/metabolism
  • Motor Neurons/physiology
  • Optogenetics/methods*
  • Synapses/physiology
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • rac1 GTP-Binding Protein/genetics*
  • rac1 GTP-Binding Protein/metabolism
PubMed: 32516597 Full text @ Dev. Cell
Axons connect neurons together, establishing the wiring architecture of neuronal networks. Axonal connectivity is largely built during embryonic development through highly constrained processes of axon guidance, which have been extensively studied. However, the inability to control axon guidance, and thus neuronal network architecture, has limited investigation of how axonal connections influence subsequent development and function of neuronal networks. Here, we use zebrafish motor neurons expressing a photoactivatable Rac1 to co-opt endogenous growth cone guidance machinery to precisely and non-invasively direct axon growth using light. Axons can be guided over large distances, within complex environments of living organisms, overriding competing endogenous signals and redirecting axons across potent repulsive barriers to construct novel circuitry. Notably, genetic axon guidance defects can be rescued, restoring functional connectivity. These data demonstrate that intrinsic growth cone guidance machinery can be co-opted to non-invasively build new connectivity, allowing investigation of neural network dynamics in intact living organisms.