Radial-glial stem cell development and plasticity in the adult zebrafish brain

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The long-term objective of my research program is to understand adult neural stem cell activity in the central nervous system of vertebrates. Most animals retain lifelong populations of adult neural stem cells in subregions of the brain, commonly known as the `neurogenic niche'. These cells produce newborn neurons throughout the life of animals, and in mammals and birds appear to play an important role in animal behaviour, learning and memory. In recent years, it has been discovered that different populations of adult neural stem cells react differently to various forms of stimuli or injury. This has proposed that adult neural stem cell populations located in different neurogenic niches may contribute to distinct functions in order to keep the central nervous system in balance. Very little however is understood towards how different populations of adult neural stem cells behave over development or under different biological contexts. This is particularly true in leading fish models, such as the zebrafish and medaka, which maintain some of the largest populations of adult neural stem cells and diversity of neurogenic niches. The proposed research will use the zebrafish model to study the activity of radial-glial brain stem cells across separate neurogenic niches and under different biological conditions. The zebrafish provides a valuable experimental system to examine these questions, owing to its adult neurogenic niches in brain structures that process both cognitive and sensory information, and remarkable neuro-regenerative potential. How populations of radial-glia change as neurogenic niches take on an adult form remains unclear. I will identify the dynamic changes in radial-glial populations from larval to adult stages and how these changes may be controlled at the molecular level. While other vertebrates, such as rodents, show a direct link between adult neural stem cells and learning species-specific behaviours, it is unknown whether this holds true in fish models. I will address this question by examining whether radial-glial populations are required to perform learning tasks in adult zebrafish. Finally, to better understand the activity of similar radial-glial stem cell types in different neurogenic niches and under different contexts, I will define radial-glial behaviour and gene regulation following enrichment and injury. Collectively, the proposed research will advance our fundamental knowledge of adult neural stem cell activity in teleost models while training at least 9 HQP. My work will serve to broaden our understanding of adult neural stem cell activity beyond the small number of vertebrates studied to date, and identify mechanisms in the zebrafish that may be present in cell populations of the central nervous system across major vertebrate and invertebrate groups. This will be important for moving towards a comparative and evolutionary understanding of the lifelong role and regulation of neural stem cells.