Neurite Growth and Guidance Responses Regulated by Nadph Oxidase-Derived Reactive Oxygen Species
NADPH oxidases (NOX) are membrane-bound multi-subunit protein complexes producing reactive oxygen species (ROS) to regulate many cellular processes. There is now emerging evidence that NOX-derived ROS also control neuronal development. In order to determine whether they play a role in specific neurite growth and guidance responses, we applied different guidance cues to cultured retinal ganglion cells (RGCs) derived from zebrafish embryos. We found that netrin-1- but not brain-derived neurotrophic factor (BDNF)-mediated neurite growth was significantly reduced when NOX was pharmacologically inhibited. Contrarily, slit2-mediated neurite retraction was abolished by NOX inhibition. These findings were confirmed with RGCs derived from mutant zebrafish that are deficient in NOX2. Furthermore, growth cone turning in response to gradients of BDNF, netrin-1, or slit2 were completely abolished, when NOX was inhibited. These results suggest that NADPH oxidases and their derived ROS are part of a signal transduction pathway downstream of specific neurite growth and guidance receptors in developing zebrafish retinal neurites.
Suter, Purdue University.
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