Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression
Abstract Background Regeneration of neurons in the central nervous system is poor in humans. In other vertebrates neural regeneration does occur efficiently and involves reactivation of developmental processes. Within the neural retina of zebrafish, Müller glia are the main stem cell source and are...
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Neural Development |
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| Online Access: | http://link.springer.com/article/10.1186/s13064-017-0089-y |
| _version_ | 1819054193419223040 |
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| author | Jeremy Ng Chi Kei Peter David Currie Patricia Regina Jusuf |
| author_facet | Jeremy Ng Chi Kei Peter David Currie Patricia Regina Jusuf |
| author_sort | Jeremy Ng Chi Kei |
| collection | DOAJ |
| description | Abstract Background Regeneration of neurons in the central nervous system is poor in humans. In other vertebrates neural regeneration does occur efficiently and involves reactivation of developmental processes. Within the neural retina of zebrafish, Müller glia are the main stem cell source and are capable of generating progenitors to replace lost neurons after injury. However, it remains largely unknown to what extent Müller glia and neuron differentiation mirror development. Methods Following neural ablation in the zebrafish retina, dividing cells were tracked using a prolonged labelling technique. We investigated to what extent extrinsic feedback influences fate choices in two injury models, and whether fate specification follows the histogenic order observed in development. Results By comparing two injury paradigms that affect different subpopulations of neurons, we found a dynamic adaptability of fate choices during regeneration. Both injuries followed a similar time course of cell death, and activated Müller glia proliferation. However, these newly generated cells were initially biased towards replacing specifically the ablated cell types, and subsequently generating all cell types as the appropriate neuron proportions became re-established. This dynamic behaviour has implications for shaping regenerative processes and ensuring restoration of appropriate proportions of neuron types regardless of injury or cell type lost. Conclusions Our findings suggest that regenerative fate processes are more flexible than development processes. Compared to development fate specification we observed a disruption in stereotypical birth order of neurons during regeneration Understanding such feedback systems can allow us to direct regenerative fate specification in injury and diseases to regenerate specific neuron types in vivo. |
| first_indexed | 2024-12-21T12:47:44Z |
| format | Article |
| id | doaj.art-78715311a6624f0f82fd9bb9ecabf479 |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-12-21T12:47:44Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-78715311a6624f0f82fd9bb9ecabf4792022-12-21T19:03:35ZengBMCNeural Development1749-81042017-07-0112111410.1186/s13064-017-0089-yFate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progressionJeremy Ng Chi Kei0Peter David Currie1Patricia Regina Jusuf2Australian Regenerative Medicine Institute, Monash UniversityAustralian Regenerative Medicine Institute, Monash UniversityAustralian Regenerative Medicine Institute, Monash UniversityAbstract Background Regeneration of neurons in the central nervous system is poor in humans. In other vertebrates neural regeneration does occur efficiently and involves reactivation of developmental processes. Within the neural retina of zebrafish, Müller glia are the main stem cell source and are capable of generating progenitors to replace lost neurons after injury. However, it remains largely unknown to what extent Müller glia and neuron differentiation mirror development. Methods Following neural ablation in the zebrafish retina, dividing cells were tracked using a prolonged labelling technique. We investigated to what extent extrinsic feedback influences fate choices in two injury models, and whether fate specification follows the histogenic order observed in development. Results By comparing two injury paradigms that affect different subpopulations of neurons, we found a dynamic adaptability of fate choices during regeneration. Both injuries followed a similar time course of cell death, and activated Müller glia proliferation. However, these newly generated cells were initially biased towards replacing specifically the ablated cell types, and subsequently generating all cell types as the appropriate neuron proportions became re-established. This dynamic behaviour has implications for shaping regenerative processes and ensuring restoration of appropriate proportions of neuron types regardless of injury or cell type lost. Conclusions Our findings suggest that regenerative fate processes are more flexible than development processes. Compared to development fate specification we observed a disruption in stereotypical birth order of neurons during regeneration Understanding such feedback systems can allow us to direct regenerative fate specification in injury and diseases to regenerate specific neuron types in vivo.http://link.springer.com/article/10.1186/s13064-017-0089-yNeural regenerationZebrafishFate biasRetinaFate specification |
| spellingShingle | Jeremy Ng Chi Kei Peter David Currie Patricia Regina Jusuf Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression Neural Development Neural regeneration Zebrafish Fate bias Retina Fate specification |
| title | Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| title_full | Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| title_fullStr | Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| title_full_unstemmed | Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| title_short | Fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| title_sort | fate bias during neural regeneration adjusts dynamically without recapitulating developmental fate progression |
| topic | Neural regeneration Zebrafish Fate bias Retina Fate specification |
| url | http://link.springer.com/article/10.1186/s13064-017-0089-y |
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