PUBLICATION
Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2
- Authors
- Terzi, A., Roeder, H., Weaver, C.J., Suter, D.M.
- ID
- ZDB-PUB-201120-129
- Date
- 2020
- Source
- Developmental Neurobiology 81(1): 3-21 (Journal)
- Registered Authors
- Suter, Daniel M., Terzi, Aslihan
- Keywords
- NADPH oxidase, Reactive oxygen species, Robo2, axon growth and guidance, hydrogen peroxide, optic chiasm, optic tectum, retinal ganglion cell, slit2
- MeSH Terms
-
- Animals
- Brain-Derived Neurotrophic Factor
- Growth Cones*
- Intracellular Signaling Peptides and Proteins/chemistry*
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- NADPH Oxidase 2*
- Netrin-1/chemistry
- Reactive Oxygen Species/chemistry*
- Receptors, Immunologic/chemistry
- Receptors, Immunologic/genetics*
- Receptors, Immunologic/metabolism
- Retinal Ganglion Cells/chemistry
- Retinal Ganglion Cells/physiology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 33191581 Full text @ Dev. Neurobiol.
Citation
Terzi, A., Roeder, H., Weaver, C.J., Suter, D.M. (2020) Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2. Developmental Neurobiology. 81(1):3-21.
Abstract
NADPH oxidases (Nox) are membrane-bound multi-subunit protein complexes producing reactive oxygen species (ROS) that regulate many cellular processes. Emerging evidence suggests that Nox-derived ROS also control neuronal development and axonal outgrowth. However, whether Nox act downstream of receptors for axonal growth and guidance cues is presently unknown. To answer this question, we cultured retinal ganglion cells (RGCs) derived from zebrafish embryos and exposed these neurons to netrin-1, slit2, and brain-derived neurotrophic factor (BDNF). To test the role of Nox in cue-mediated growth and guidance, we either pharmacologically inhibited Nox or investigated neurons from mutant fish that are deficient in Nox2. We found that slit2-mediated growth cone collapse, and axonal retraction was eliminated by Nox inhibition. Though we did not see an effect of either BDNF or netrin-1 on growth rates, growth in the presence of netrin-1 was reduced by Nox inhibition. Furthermore, attractive and repulsive growth cone turning in response to gradients of BDNF, netrin-1, and slit2, respectively, were eliminated when Nox was inhibited in vitro. ROS biosensor imaging showed that slit2 treatment increased growth cone hydrogen peroxide levels via mechanisms involving Nox2 activation. We also investigated the possible relationship between Nox2 and slit2/Robo2 signaling in vivo. astray/nox2 double heterozygote larvae exhibited decreased area of tectal innervation as compared to individual heterozygotes, suggesting both Nox2 and Robo2 are required for establishment of retinotectal connections. Our results provide evidence that Nox2 acts downstream of slit2/robo2 by mediating growth and guidance of developing zebrafish RGC neurons.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping