Conditional and biased regeneration of cone photoreceptor types in the zebrafish retina

D'Orazi, F.D., Suzuki, S.C., Darling, N., Wong, R.O., Yoshimatsu, T.
The Journal of comparative neurology   528(17): 2816-2830 (Journal)
Registered Authors
Wong, Rachel
cone genesis, neuronal repair, nitro-reductase cell ablation, photoreceptor cell proliferation, retinal regeneration, zebrafish photoreceptors
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation/physiology*
  • Nerve Regeneration/physiology*
  • Neuroglia/chemistry
  • Neuroglia/metabolism*
  • Retina/chemistry
  • Retina/metabolism
  • Retinal Cone Photoreceptor Cells/chemistry
  • Retinal Cone Photoreceptor Cells/metabolism*
  • Zebrafish
32342988 Full text @ J. Comp. Neurol.
A major challenge in regenerative medicine is replacing cells lost through injury or disease. While significant progress has been made, much remains unknown about the accuracy of native regenerative programs in cell replacement. Here, we capitalized on the regenerative capacity and stereotypic retinal organization of zebrafish to determine the specificity with which retinal Müller glial cells replace lost neuronal cell types. By utilizing a targeted genetic ablation technique, we restricted death to all or to distinct cone photoreceptor types (red, blue or UV-sensitive cones), enabling us to compare the composition of cones that are regenerated. We found that Müller glia produce cones of all types upon non-discriminate ablation of these photoreceptors, or upon selective ablation of red or UV cones. Pan-ablation of cones led to regeneration of the various cone types in relative abundances that resembled those of non-ablated controls, i.e. red>green>UV ~ blue cones. Moreover, selective loss of red or UV cones biased production toward the cone type that was ablated. In contrast, ablation of blue cones alone largely failed to induce cone production at all, although it did induce cell division in Müller glia. The failure to produce cones upon selective elimination of blue cones may be due to their low abundance compared to other cone types. Alternatively, it may be that blue cone death alone does not trigger a change in progenitor competency to support cone genesis. Our findings add to the growing notion that cell replacement during regeneration does not perfectly mimic programs of cell generation during development. This article is protected by copyright. All rights reserved.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes