The role of Nox-derived Reactive Oxygen Species in Axonal Growth and Guidance

Reactive oxygen species (ROS) are well-known for their detrimental effects leading to oxidative stress, cell death, aging, and degenerative disorders. However, there is increasing evidence that ROS are also specifically produced to regulate cellular processes including cell proliferation, differentiation, and migration. Our group has recently demonstrated that ROS are also critical for neurite outgrowth and actin-dependent growth cone motility in cultured Aplysia neurons. In order to investigate the role of ROS derived from NADPH oxidase (Nox), a major ROS source, we moved our research into a new model system, developing zebrafish embryos. Using pharmacological inhibition of Nox as well as zebrafish that are deficient in specific Nox isoforms, we found that ROS produced by Nox2 are critical for the development of retinotectal connections and response of retinal ganglion cell growth cones to guidance cues such as slit2. Thus, our results suggest that Nox-derived ROS play a critical role in neuronal development, especially in axonal growth and guidance.

Learning Objectives:

1. Recognize ROS as signaling molecules in nervous system development

2. Explain the value of Aplysia and zebrafish as model systems for in vitro and in vivo studies of axonal growth and guidance