Analysis of the astray/robo2 Zebrafish Mutant Reveals that Degenerating Tracts Do Not Provide Strong Guidance Cues for Regenerating Optic Axons
- Wyatt, C., Ebert, A., Reimer, M.M., Rasband, K., Hardy, M., Chien, C.B., Becker, T., and Becker, C.G.
- The Journal of neuroscience : the official journal of the Society for Neuroscience 30(41): 13838-13849 (Journal)
- Registered Authors
- Becker, Catherina G., Becker, Thomas, Chien, Chi-Bin, Ebert, Anselm, Hardy, Melissa, Rasband, Kendall, Reimer, Michell M., Wyatt, Cameron
- MeSH Terms
- In Situ Hybridization
- Nerve Degeneration/metabolism*
- Nerve Degeneration/pathology
- Nerve Regeneration/physiology*
- Optic Nerve/pathology
- Optic Nerve/physiology*
- Receptors, Immunologic/genetics
- Receptors, Immunologic/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 20943924 Full text @ J. Neurosci.
Wyatt, C., Ebert, A., Reimer, M.M., Rasband, K., Hardy, M., Chien, C.B., Becker, T., and Becker, C.G. (2010) Analysis of the astray/robo2 Zebrafish Mutant Reveals that Degenerating Tracts Do Not Provide Strong Guidance Cues for Regenerating Optic Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(41):13838-13849.
During formation of the optic projection in astray/robo2 mutant zebrafish, optic axons exhibit rostrocaudal pathfinding errors, ectopic midline crossing and increased terminal arbor size. Here we show that these errors persist into adulthood, even when robo2 function is conditionally reduced only during initial formation of the optic projection. Adult errors include massive ectopic optic tracts in the telencephalon. During optic nerve regeneration in astray/robo2 animals, these tracts are not repopulated and ectopic midline crossing is reduced compared with unlesioned mutants. This is despite a comparable macrophage/microglial response and upregulation of contactin1a in oligodendrocytes of entopic and ectopic tracts. However, other errors, such as expanded termination areas and ectopic growth into the tectum, were frequently recommitted by regenerating optic axons. Retinal ganglion cells with regenerating axons reexpress robo2 and expression of slit ligands is maintained in some areas of the adult optic pathway. However, slit expression is reduced rostral and caudal to the chiasm, compared with development and ubiquitous overexpression of Slit2 did not elicit major pathfinding phenotypes. This shows that (1) there is not an efficient correction mechanism for large-scale pathfinding errors of optic axons during development; (2) degenerating tracts do not provide a strong guidance cue for regenerating optic axons in the adult CNS, unlike the PNS; and (3) robo2 is less important for pathfinding of optic axons during regeneration than during development.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes