Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2
| العنوان: | Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2 |
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| المؤلفون: | Haley Roeder, Aslihan Terzi, Daniel M. Suter, Cory J. Weaver |
| المصدر: | Dev Neurobiol |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Retinal Ganglion Cells, 0301 basic medicine, Growth Cones, Retinal ganglion, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Neurotrophic factors, medicine, Animals, Receptors, Immunologic, Growth cone, Receptor, Zebrafish, chemistry.chemical_classification, Reactive oxygen species, NADPH oxidase, biology, Brain-Derived Neurotrophic Factor, Intracellular Signaling Peptides and Proteins, Netrin-1, Zebrafish Proteins, biology.organism_classification, Cell biology, 030104 developmental biology, medicine.anatomical_structure, nervous system, Retinal ganglion cell, chemistry, NADPH Oxidase 2, cardiovascular system, biology.protein, Reactive Oxygen Species, 030217 neurology & neurosurgery, circulatory and respiratory physiology |
| الوصف: | 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 were 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. |
| تدمد: | 1932-846X 1932-8451 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::733b2bf530a2d0a126ec91545c5c2668Test https://doi.org/10.1002/dneu.22791Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....733b2bf530a2d0a126ec91545c5c2668 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1932846X 19328451 |
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