Uncovering the spectrum of adult zebraﬁsh neural stem cell cycle regulators

Front. Cell Dev. Biol., 2022 · DOI: 10.3389/fcell.2022.941893 · Published: June 29, 2022

Regenerative Medicine Neurology Research Methodology & Design

Simple Explanation

Adult neural stem and progenitor cells (aNSPCs) are present throughout life in teleost models, residing in various stem cell niches within the brain and spinal cord. These fish maintain developmental stem cell populations, including neuro-epithelial cells (NECs) and radial-glial cells (RGCs), with RGCs existing in cycling or quiescent states while NECs continuously divide. Growing evidence suggests that aNSPCs are sensitive to environmental cues, social interactions, nutrient availability, and neurotrauma. These stimuli appear to act as triggers to either turn on normally dormant aNSPCs or modulate constitutive rates of niche-specific cell cycle behavior. This review synthesizes current knowledge on aNSPCs from studies investigating the zebraﬁsh CNS, highlighting emerging cell cycle regulators and outstanding questions to advance the field of stem cell biology.

Study Duration

Not specified

Participants

Zebrafish

Evidence Level

Review

Key Findings

1
Social interactions, stress, hormones, diet, and sensory stimuli significantly influence aNSPC activity in the zebrafish CNS.
2
Environmental enrichment and specific visual cues can induce changes in long-term aNSPC activity.
3
Following CNS damage, quiescent RGCs are awakened to re-enter the cell cycle and repopulate lost neuronal subtypes, with constitutively active NECs also contributing to repair.

Research Summary

This review examines the factors that regulate adult neural stem and progenitor cell (aNSPC) cell cycle dynamics in teleosts, particularly focusing on studies using the zebraﬁsh model. It highlights how environmental stimuli can modulate cell proliferation rates and discusses outstanding questions and techniques to advance the understanding of aNSPCs under physiological and pathological conditions. The review also summarizes how aNSPCs respond to CNS damage and neurodegenerative diseases, offering insight into the balance between factors in the damaged stem cell niche and the intrinsic regenerative programs of distinct aNSPC populations.

Practical Implications

Understanding aNSPC Regulation

Defining the stimuli that influence RGC and NEC proliferation and identifying the molecular regulators responsible will strengthen our understanding of the connection between aNSPC activity and their biological significance.

Developing Therapies for CNS Repair

The zebraﬁsh model offers a platform for drug screening to identify therapeutics to test in mammals to improve spinal cord repair, potentially leading to new treatments for CNS injuries.

Investigating Neurodegenerative Diseases

The zebraﬁsh model's applicability to Alzheimer's and Parkinson's disease research provides avenues to elucidate aNSPC responses in neurodegeneration, which may uncover novel therapeutic targets.

Study Limitations

1
The precise mechanisms by which specific stimuli push quiescent RGCs into a cycling state remain unclear.
2
The molecular signatures of similar aNSPCs in different adult niches and their correlation with varied responses to environmental or injury-induced cues are not fully understood.
3
Knowledge of the stem cell niche is mostly limited to the role of the immune response post-injury, with the involvement of neighboring cells, extracellular matrix, and vasculature requiring further study.

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