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Stab Wound Injury Model of the Adult Optic Tectum Using Zebrafish and Medaka for the Comparative Analysis of Regenerative Capacity
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Midbrain tectal stem cells display diverse regenerative capacities in zebrafish
Benjamin W Lindsey1,2, Georgia E Aitken1, Jean K Tang1
1Australian Regenerative Medicine Institute, Monash University Clayton Campus, Clayton, Victoria, 3800, Australia.
Scientific Reports
|March 16, 2019
Summary
Quiescent radial-glia (qRG) in zebrafish brains show limited neuronal repair post-injury. Instead, neuro-epithelial-like progenitors amplify regeneration, indicating diverse stem cell roles in brain repair.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Developmental Biology
Background:
- Brain regeneration mechanisms involving diverse stem and progenitor cells are not fully understood.
- Radial-glia (RG) and neuro-epithelial-like (NE) cells are known contributors to neuronal repair in regenerative vertebrates like zebrafish.
- The specific role of quiescent RG (qRG) in brain repair post-injury remains unclear, as not all RG function as neural stem/progenitor cells during homeostasis.
Purpose of the Study:
- To investigate the function of quiescent radial-glia (qRG) during brain regeneration after injury.
- To analyze the proliferative behavior, differentiation potential, and Wnt/β-catenin signaling of qRG post-injury.
- To understand the contribution of different stem/progenitor populations to neurogenesis following brain damage.
Main Methods:
- Performed stab lesion in the adult zebrafish midbrain tectum to target homeostatic qRG.
- Utilized EdU-labeling to assess cell proliferation and progeny fate.
- Measured Wnt/β-catenin signaling levels in response to injury.
- Manipulated Wnt signaling to determine its role in the proliferative response.
Main Results:
- A small subset of qRG proliferated post-injury (pRG), but their progeny were restricted to RG lineage.
- Injury significantly promoted proliferation of NE progenitors in the tectal marginal zone (TMZi), leading to amplified neurogenesis.
- Wnt/β-catenin signaling increased in TMZi post-injury but remained at homeostatic levels in qRG/pRG.
- Wnt signaling attenuation did not affect the post-injury proliferative response, indicating it was Wnt-independent.
Conclusions:
- Quiescent RG in the zebrafish tectum have a limited capacity for neuronal repair after injury.
- Neuro-epithelial-like progenitors are the primary drivers of amplified neurogenesis and tissue repair in this model.
- These findings highlight the diverse functions of RG in the zebrafish brain and suggest that endogenous stem cell compartments compensate for tissue loss by enhancing homeostatic growth.
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